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      {
         "type" : "Publication",
         "id"   : "https://puma.ub.uni-stuttgart.de/bibtex/222bd48b9c5df6375654727c982125149/testusersimtech",         
         "tags" : [
            "EXC2075","PN2"
         ],
         
         "intraHash" : "22bd48b9c5df6375654727c982125149",
         "interHash" : "f87d2c872f2e6f474113b724ada23083",
         "label" : "A benchmark of muscle models to length changes great and small",
         "user" : "testusersimtech",
         "description" : "linked to Projekt Adires",
         "date" : "2025-01-27 13:09:00",
         "changeDate" : "2025-01-27 13:09:00",
         "count" : 16,
         "pub-type": "article",
         "journal": "Journal of the Mechanical Behavior of Biomedical Materials",
         "year": "2024", 
         "url": "https://www.sciencedirect.com/science/article/pii/S1751616124003722?via%3Dihub", 
         
         "author": [ 
            "Matthew Millard","Norman Stutzig","Jörg Fehr","Tobias Siebert"
         ],
         "authors": [
         	
            	{"first" : "Matthew",	"last" : "Millard"},
            	{"first" : "Norman",	"last" : "Stutzig"},
            	{"first" : "Jörg",	"last" : "Fehr"},
            	{"first" : "Tobias",	"last" : "Siebert"}
         ],
         "volume": "160","pages": "106740","abstract": "Digital human body models are used to simulate injuries that occur as a result of vehicle collisions, vibration, sports, and falls. Given enough time the body\u2019s musculature can generate force, affect the body\u2019s movements, and change the risk of some injuries. The finite-element code LS-DYNA is often used to simulate the movements and injuries sustained by the digital human body models as a result of an accident. In this work, we evaluate the accuracy of the three muscle models in LS-DYNA (MAT_156, EHTM, and the VEXAT) when simulating a range of experiments performed on isolated muscle: force-length-velocity experiments on maximally and sub-maximally stimulated muscle, active-lengthening experiments, and vibration experiments. The force-length-velocity experiments are included because these conditions are typical of the muscle activity that precedes an accident, while the active-lengthening and vibration experiments mimic conditions that can cause injury. The three models perform similarly during the maximally and sub-maximally activated force-length-velocity experiments, but noticeably differ in response to the active-lengthening and vibration experiments. The VEXAT model is able to generate the enhanced forces of biological muscle during active lengthening, while both the MAT_156 and EHTM produce too little force. In response to vibration, the stiffness and damping of the VEXAT model closely follows the experimental data while the MAT_156 and EHTM models differ substantially. The accuracy of the VEXAT model comes from two additional mechanical structures that are missing in the MAT_156 and EHTM models: viscoelastic cross-bridges, and an active titin filament. To help others build on our work we have made our simulation code publicly available.",
         "language" : "English",
         
         "doi" : "10.1016/j.jmbbm.2024.106740",
         
         "bibtexKey": "millard2024benchmark"

      }
,
      {
         "type" : "Publication",
         "id"   : "https://puma.ub.uni-stuttgart.de/bibtex/2112b47e516f3b08e53d295d89027127a/testusersimtech",         
         "tags" : [
            "EXC2075","PN2","PN2-8Siebert","selected"
         ],
         
         "intraHash" : "112b47e516f3b08e53d295d89027127a",
         "interHash" : "7118ef30d9e0d0109338f9b611d56769",
         "label" : "Impact of contraction intensity and ankle joint angle on calf muscle fascicle length and pennation angle during isometric and dynamic contractions",
         "user" : "testusersimtech",
         "description" : "",
         "date" : "2025-01-27 13:09:00",
         "changeDate" : "2025-01-27 13:09:00",
         "count" : 6,
         "pub-type": "article",
         "journal": "Scientific Reports",
         "year": "2024", 
         "url": "https://doi.org/10.1038/s41598-024-75795-2", 
         
         "author": [ 
            "Corinna Coenning","Volker Rieg","Tobias Siebert","Veit Wank"
         ],
         "authors": [
         	
            	{"first" : "Corinna",	"last" : "Coenning"},
            	{"first" : "Volker",	"last" : "Rieg"},
            	{"first" : "Tobias",	"last" : "Siebert"},
            	{"first" : "Veit",	"last" : "Wank"}
         ],
         
         "editor": [ 
            "Tobias Siebert"
         ],
         "editors": [
         	
            	{"first" : "Tobias",	"last" : "Siebert"}
         ],
         "volume": "14","number": "1","pages": "24929","abstract": "During muscle contraction, not only are the fascicles shortening but also the pennation angle changes, which leads to a faster contraction of the muscle than of its fascicles. This phenomenon is called muscle gearing, and it has a direct influence on the force output of the muscle. There are few studies showing pennation angle changes during isometric and concentric contractions for different contraction intensities and muscle lengths. Therefore, the aim was to determine these influences over a wide range of contraction intensities and ankle joint angles for human triceps surae. Additionally, the influence of contraction intensity and ankle joint angle on muscle gearing was evaluated. Ten sport students performed concentric and isometric contractions with intensities between 0 and 90\\% of the maximum voluntary contraction and ankle joint angles from 50° to 120°. During these contractions, the m. gastrocnemius medialis and lateralis and the m. soleus were recorded via ultrasound imaging. A nonlinear relationship between fascicle length and pennation angle was discovered, which can be described with a quadratic fit for each of the muscles during isometric contraction. A nearly identical relationship was detected during dynamic contraction. The muscle gearing increased almost linearly with contraction intensity and ankle joint angle.",
         "issn" : "2045-2322",
         
         "doi" : "10.1038/s41598-024-75795-2",
         
         "bibtexKey": "Coenning2024"

      }
,
      {
         "type" : "Publication",
         "id"   : "https://puma.ub.uni-stuttgart.de/bibtex/2c95bd672eec94118623f036030864e68/testusersimtech",         
         "tags" : [
            "EXC2075","PN2","selected"
         ],
         
         "intraHash" : "c95bd672eec94118623f036030864e68",
         "interHash" : "958da81d5faeafe01668d01f4a237c19",
         "label" : "Role of Rotated Head Postures on Volunteer Kinematics and Muscle Activity in Braking Scenarios Performed on a Driving Simulator",
         "user" : "testusersimtech",
         "description" : "linked to Adires",
         "date" : "2025-01-27 13:09:00",
         "changeDate" : "2025-01-27 13:09:00",
         "count" : 5,
         "pub-type": "article",
         "journal": "Annals of Biomedical Engineering",
         "year": "2024", 
         "url": "https://link.springer.com/article/10.1007/s10439-022-03087-9", 
         
         "author": [ 
            "Fabian Kempter","Lorena Lantella","Norman Stutzig","Jörg Fehr","Tobias Siebert"
         ],
         "authors": [
         	
            	{"first" : "Fabian",	"last" : "Kempter"},
            	{"first" : "Lorena",	"last" : "Lantella"},
            	{"first" : "Norman",	"last" : "Stutzig"},
            	{"first" : "Jörg",	"last" : "Fehr"},
            	{"first" : "Tobias",	"last" : "Siebert"}
         ],
         "volume": "51","pages": "771\u2013782","abstract": "Occupants exposed to low or moderate crash events can already suffer from whiplash-associated disorders leading to severe and long-lasting symptoms. However, the underlying injury mechanisms and the role of muscle activity are not fully clear. Potential increases in injury risk of non-nominal postures, i.e., rotated head, cannot be evaluated in detail due to the lack of experimental data. Examining changes in neck muscle activity to hold and stabilize the head in a rotated position during pre-crash scenarios might provide a deeper understanding of muscle reflex contributions and injury mechanisms. In this study, the influence of two different head postures (nominal vs. rotation of the head by about 63\u2009±\u20099° to the right) on neck muscle activity and head kinematics was investigated in simulated braking experiments inside a driving simulator. The braking scenario was implemented by visualization of the virtual scene using head-mounted displays and a combined translational-rotational platform motion. Kinematics of seventeen healthy subjects was tracked using 3D motion capturing. Surface electromyography were used to quantify muscle activity of left and right sternocleidomastoideus (SCM) and trapezius (TRP) muscles. The results show clear evidence that rotated head postures affect the static as well as the dynamic behavior of muscle activity during the virtual braking event. With head turned to the right, the contralateral left muscles yielded higher base activation and delayed muscle onset times. In contrast, right muscles had much lower activations and showed no relevant changes in muscle activation between nominal and rotated head position. The observed delayed muscle onset times and increased asymmetrical muscle activation patterns in the rotated head position are assumed to affect injury mechanisms. This could explain the prevalence of rotated head postures during a crash reported by patients suffering from WAD. The results can be used for validating the active behavior of human body models in braking simulations with nominal and rotated head postures, and to gain a deeper understanding of neck injury mechanisms.",
         "doi" : "10.1007/s10439-022-03087-9",
         
         "bibtexKey": "noauthororeditor2024rotated"

      }
,
      {
         "type" : "Publication",
         "id"   : "https://puma.ub.uni-stuttgart.de/bibtex/21ba781404619589ae488cb37851e45a6/testusersimtech",         
         "tags" : [
            "EXC2075","PN2","PN2-6(II)","seelcted"
         ],
         
         "intraHash" : "1ba781404619589ae488cb37851e45a6",
         "interHash" : "a09cf079d6fccb01943e3dbb28409185",
         "label" : "Modeling Enzyme Kinetics: Current Challenges and Future Perspectives for Biocatalysis",
         "user" : "testusersimtech",
         "description" : "",
         "date" : "2025-01-27 13:09:00",
         "changeDate" : "2025-01-27 13:09:00",
         "count" : 6,
         "pub-type": "article",
         "journal": "Biochemistry","booktitle": "Biochemistry","publisher":"American Chemical Society",
         "year": "2024", 
         "url": "https://doi.org/10.1021/acs.biochem.4c00501", 
         
         "author": [ 
            "Jürgen Pleiss"
         ],
         "authors": [
         	
            	{"first" : "Jürgen",	"last" : "Pleiss"}
         ],
         "volume": "63","number": "20","pages": "2533-2541",
         "orcid" : "0000-0003-1045-8202",
         
         "issn" : "00062960",
         
         "comment" : "doi: 10.1021/acs.biochem.4c00501",
         
         "doi" : "10.1021/acs.biochem.4c00501",
         
         "bibtexKey": "pleiss2024modeling"

      }
,
      {
         "type" : "Publication",
         "id"   : "https://puma.ub.uni-stuttgart.de/bibtex/24a122061de06137fc1895607c95226f1/testusersimtech",         
         "tags" : [
            "EXC2075","PN2","PN2-6","selected"
         ],
         
         "intraHash" : "4a122061de06137fc1895607c95226f1",
         "interHash" : "c95189d52d2ce9bdf72132f187c89b32",
         "label" : "Research Data Management in Simulation Science: Infrastructure, Tools, and Applications",
         "user" : "testusersimtech",
         "description" : "",
         "date" : "2025-01-27 13:09:00",
         "changeDate" : "2025-01-27 13:09:00",
         "count" : 11,
         "pub-type": "article",
         "journal": "Datenbank-Spektrum",
         "year": "2024", 
         "url": "https://doi.org/10.1007/s13222-024-00475-4", 
         
         "author": [ 
            "Bernd Flemisch","Sibylle Hermann","Melanie Herschel","Dirk Pflüger","Jürgen Pleiss","Jan Range","Sarbani Roy","Makoto Takamoto","Benjamin Uekermann"
         ],
         "authors": [
         	
            	{"first" : "Bernd",	"last" : "Flemisch"},
            	{"first" : "Sibylle",	"last" : "Hermann"},
            	{"first" : "Melanie",	"last" : "Herschel"},
            	{"first" : "Dirk",	"last" : "Pflüger"},
            	{"first" : "Jürgen",	"last" : "Pleiss"},
            	{"first" : "Jan",	"last" : "Range"},
            	{"first" : "Sarbani",	"last" : "Roy"},
            	{"first" : "Makoto",	"last" : "Takamoto"},
            	{"first" : "Benjamin",	"last" : "Uekermann"}
         ],
         "volume": "24","pages": "97\u2013105","abstract": "Research Data Management (RDM) has gained significant traction in recent years, being essential to allowing research data to be, e.g., findable, accessible, interoperable, and reproducible (FAIR), thereby fostering collaboration or accelerating scientific findings. We present solutions for RDM developed within the DFG-Funded Cluster of Excellence EXC2075 Data-Integrated Simulation Science (SimTech). After an introduction to the scientific context and challenges faced by simulation scientists, we outline the general data management infrastructure and present tools that address these challenges. Exemplary domain applications demonstrate the use and benefits of the proposed data management software solutions. These are complemented by additional measures for enablement and dissemination to foster the adoption of these techniques.",
         "orcid" : "0000-0003-1045-8202",
         
         "issn" : "16101995",
         
         "refid" : "Flemisch2024",
         
         "doi" : "10.1007/s13222-024-00475-4",
         
         "bibtexKey": "flemisch2024research"

      }
,
      {
         "type" : "Publication",
         "id"   : "https://puma.ub.uni-stuttgart.de/bibtex/26d49d6168fbd9ade1c6bc3cb269fa09f/testusersimtech",         
         "tags" : [
            "EXC2075","PN2","PN2-6","PN2-6(II)","selected"
         ],
         
         "intraHash" : "6d49d6168fbd9ade1c6bc3cb269fa09f",
         "interHash" : "a63975933e5fae2b566e573464f01848",
         "label" : "CANDy: Automated analysis of domain architectures in carbohydrate-active enzymes",
         "user" : "testusersimtech",
         "description" : "",
         "date" : "2024-09-16 14:37:42",
         "changeDate" : "2024-09-16 14:37:42",
         "count" : 6,
         "pub-type": "article",
         "journal": "PLOS ONE","publisher":"Public Library of Science",
         "year": "2024", 
         "url": "https://doi.org/10.1371/journal.pone.0306410", 
         
         "author": [ 
            "Alex Windels","Jorick Franceus","Jürgen Pleiss","Tom Desmet"
         ],
         "authors": [
         	
            	{"first" : "Alex",	"last" : "Windels"},
            	{"first" : "Jorick",	"last" : "Franceus"},
            	{"first" : "Jürgen",	"last" : "Pleiss"},
            	{"first" : "Tom",	"last" : "Desmet"}
         ],
         "volume": "19","number": "7","pages": "1-16","abstract": "Carbohydrate-active enzymes (CAZymes) can be found in all domains of life and play a crucial role in metabolic and physiological processes. CAZymes often possess a modular structure, comprising not only catalytic domains but also associated domains such as carbohydrate-binding modules (CBMs) and linker domains. By exploring the modular diversity of CAZy families, catalysts with novel properties can be discovered and further insight in their biological functions and evolutionary relationships can be obtained. Here we present the carbohydrate-active enzyme domain analysis tool (CANDy), an assembly of several novel scripts, tools and databases that allows users to analyze the domain architecture of all protein sequences in a given CAZy family. CANDy\u2019s usability is shown on glycoside hydrolase family 48, a small yet underexplored family containing multi-domain enzymes. Our analysis reveals the existence of 35 distinct domain assemblies, including eight known architectures, with the remaining assemblies awaiting characterization. Moreover, we substantiate the occurrence of horizontal gene transfer from prokaryotes to insect orthologs and provide evidence for the subsequent removal of auxiliary domains, likely through a gene fission event. CANDy is available at https://github.com/PyEED/CANDy.",
         "orcid" : "0000-0003-1045-8202",
         
         "doi" : "10.1371/journal.pone.0306410",
         
         "bibtexKey": "10.1371/journal.pone.0306410"

      }
,
      {
         "type" : "Publication",
         "id"   : "https://puma.ub.uni-stuttgart.de/bibtex/213d1c527b422f0c2fbfb26d98885b1f6/testusersimtech",         
         "tags" : [
            "EXC2075","PN2","selected"
         ],
         
         "intraHash" : "13d1c527b422f0c2fbfb26d98885b1f6",
         "interHash" : "1a1ddb22b3fc4a98ff638b17f957aa71",
         "label" : "Force re-development after shortening reveals a role for titin in stretch-shortening performance enhancement in skinned muscle fibres",
         "user" : "testusersimtech",
         "description" : "",
         "date" : "2024-09-12 12:02:31",
         "changeDate" : "2024-09-12 12:02:31",
         "count" : 6,
         "pub-type": "article",
         "journal": "Journal of Experimental Biology","publisher":"The Company of Biologists",
         "year": "2024", 
         "url": "http://dx.doi.org/10.1242/jeb.247377", 
         
         "author": [ 
            "André Tomalka","Sven Weidner","Daniel Hahn","Wolfgang Seiberl","Tobias Siebert"
         ],
         "authors": [
         	
            	{"first" : "André",	"last" : "Tomalka"},
            	{"first" : "Sven",	"last" : "Weidner"},
            	{"first" : "Daniel",	"last" : "Hahn"},
            	{"first" : "Wolfgang",	"last" : "Seiberl"},
            	{"first" : "Tobias",	"last" : "Siebert"}
         ],
         
         "editor": [ 
            "Tobias Siebert"
         ],
         "editors": [
         	
            	{"first" : "Tobias",	"last" : "Siebert"}
         ],
         "abstract": "Stretch-shortening cycles (SSCs) involve muscle lengthening (eccentric contractions) instantly followed by shortening (concentric contractions). This combination enhances force, work, and power output compared to pure shortening (SHO), which is known as SSC-effect. Recent evidence indicates both cross-bridge-based (XB) and non-cross-bridge-based (non-XB, e.g., titin) structures contribute to this effect. This study analyzed force re-development following SSCs and SHO to gain further insight into the roles of XB and non-XB structures regarding the SSC-effect. Experiments were conducted on rat soleus muscle fibres (n=16) with different SSC velocities (30%, 60%, 85% of maximum shortening velocity) and constant stretch-shortening magnitudes (18% of optimum length). The XB inhibitor blebbistatin was used to distinguish between XB and non-XB contributions to force generation. Results showed SSCs led to significantly greater (1.02±.15 vs. 0.68±.09 [ΔF/Δt]; t(62)=8.61, p<.001, d=2.79) and faster (75 ms vs. 205 [ms]; t(62) = -6.37, p<.001, d=-1.48) force re-development compared to SHO in the control treatment. In the blebbistatin treatment, SSCs still resulted in greater (.11±.03 vs. .06±.01 [ΔF/Δt]; t(62) = 8.00, p<.001, d=2.24) and faster (3010±1631 vs. 7916±3230 [ms]; t(62) = -8.00, p<.001, d=-1.92) force re-development compared to SHO. These findings deepen our understanding of the SSC-effect, underscoring the involvement of non-XB structures like titin in modulating force production. This modulation likely involves complex mechanosensory coupling from stretch to signal transmission during muscle contraction.",
         "issn" : "1477-9145",
         
         "doi" : "10.1242/jeb.247377",
         
         "bibtexKey": "Tomalka_2024"

      }
,
      {
         "type" : "Publication",
         "id"   : "https://puma.ub.uni-stuttgart.de/bibtex/2cec8a111dfdbe3d95f26e49b60772376/testusersimtech",         
         "tags" : [
            "EXC2075","PN2","PN2-8Siebert","selected"
         ],
         
         "intraHash" : "cec8a111dfdbe3d95f26e49b60772376",
         "interHash" : "2a047a874b55c8f5880dca4f43c710f8",
         "label" : "Note on hydrostatic skeletons: Muscles operating within a pressurized environment",
         "user" : "testusersimtech",
         "description" : "",
         "date" : "2024-08-09 07:49:09",
         "changeDate" : "2024-08-09 07:49:09",
         "count" : 6,
         "pub-type": "article",
         "journal": "Biology Open",
         "year": "2024", 
         "url": "https://journals.biologists.com/bio/article/doi/10.1242/bio.060318/352248", 
         
         "author": [ 
            "Reinhard Blickhan","Tobias Siebert"
         ],
         "authors": [
         	
            	{"first" : "Reinhard",	"last" : "Blickhan"},
            	{"first" : "Tobias",	"last" : "Siebert"}
         ],
         
         "editor": [ 
            "Tobias Siebert"
         ],
         "editors": [
         	
            	{"first" : "Tobias",	"last" : "Siebert"}
         ],
         "pages": "bio.060318","abstract": "Muscles and muscle fibers are volume-constant constructs that deform when contracted and develop internal pressures. However, muscles embedded in hydrostatic skeletons are also exposed to external pressures generated by their activity. For two examples, the pressure generation in spiders and in annelids, we used simplified biomechanical models to demonstrate that high intracellular pressures diminishing the resulting tensile stress of the muscle fibers are avoided in the hydrostatic skeleton. The findings are relevant for a better understanding of the design and functionality of biological hydrostatic skeletons.",
         "eprint" : "https://journals.biologists.com/bio/article-pdf/doi/10.1242/bio.060318/3467476/bio060318.pdf",
         
         "issn" : "2046-6390",
         
         "doi" : "10.1242/bio.060318",
         
         "bibtexKey": "10.1242/bio.060318"

      }
,
      {
         "type" : "Publication",
         "id"   : "https://puma.ub.uni-stuttgart.de/bibtex/23703361ba5364a5c2d4588e2de1b7f6e/testusersimtech",         
         "tags" : [
            "EXC2075","PN2","PN2A-1","selected"
         ],
         
         "intraHash" : "3703361ba5364a5c2d4588e2de1b7f6e",
         "interHash" : "91b7f9a1d1c44b2548f31012f256c179",
         "label" : "Impact of lengthening velocity on the generation of eccentric force by slow-twitch muscle fibers in long stretches",
         "user" : "testusersimtech",
         "description" : "",
         "date" : "2024-08-09 07:49:09",
         "changeDate" : "2024-08-09 07:49:09",
         "count" : 6,
         "pub-type": "article",
         "journal": "Pfluegers Archiv - European Journal of Physiology",
         "year": "2024", 
         "url": "https://doi.org/10.1007/s00424-024-02991-4", 
         
         "author": [ 
            "Sven Weidner","André Tomalka","Christian Rode","Tobias Siebert"
         ],
         "authors": [
         	
            	{"first" : "Sven",	"last" : "Weidner"},
            	{"first" : "André",	"last" : "Tomalka"},
            	{"first" : "Christian",	"last" : "Rode"},
            	{"first" : "Tobias",	"last" : "Siebert"}
         ],
         
         "editor": [ 
            "Tobias Siebert"
         ],
         "editors": [
         	
            	{"first" : "Tobias",	"last" : "Siebert"}
         ],
         "abstract": "After an initial increase, isovelocity elongation of a muscle fiber can lead to diminishing (referred to as Give in the literature) and subsequently increasing force. How the stretch velocity affects this behavior in slow-twitch fibers remains largely unexplored. Here, we stretched fully activated individual rat soleus muscle fibers from 0.85 to 1.3 optimal fiber length at stretch velocities of 0.01, 0.1, and 1 maximum shortening velocity, vmax, and compared the results with those of rat EDL fast-twitch fibers obtained in similar experimental conditions. In soleus muscle fibers, Give was 7\\%, 18\\%, and 44\\% of maximum isometric force for 0.01, 0.1, and 1 vmax, respectively. As in EDL fibers, the force increased nearly linearly in the second half of the stretch, although the number of crossbridges decreased, and its slope increased with stretch velocity. Our findings are consistent with the concept of a forceful detachment and subsequent crossbridge reattachment in the stretch's first phase and a strong viscoelastic titin contribution to fiber force in the second phase of the stretch. Interestingly, we found interaction effects of stretch velocity and fiber type on force parameters in both stretch phases, hinting at fiber type-specific differences in crossbridge and titin contributions to eccentric force. Whether fiber type-specific combined XB and non-XB models can explain these effects or if they hint at some not fully understood properties of muscle contraction remains to be shown. These results may stimulate new optimization perspectives in sports training and provide a better understanding of structure--function relations of muscle proteins.",
         "issn" : "1432-2013",
         
         "doi" : "10.1007/s00424-024-02991-4",
         
         "bibtexKey": "Weidner2024"

      }
,
      {
         "type" : "Publication",
         "id"   : "https://puma.ub.uni-stuttgart.de/bibtex/21c09ad3a57d45986105107c77d0da5cf/testusersimtech",         
         "tags" : [
            "EXC2075","PN2","PN2-8Siebert","selected"
         ],
         
         "intraHash" : "1c09ad3a57d45986105107c77d0da5cf",
         "interHash" : "539e1f9768e937f368f3546f4de55813",
         "label" : "Determination of muscle shape deformations of the tibialis anterior during dynamic contractions using 3D ultrasound",
         "user" : "testusersimtech",
         "description" : "",
         "date" : "2024-08-09 07:49:09",
         "changeDate" : "2024-08-09 07:49:09",
         "count" : 7,
         "pub-type": "article",
         "journal": "Frontiers in Bioengineering and Biotechnology",
         "year": "2024", 
         "url": "https://www.frontiersin.org/articles/10.3389/fbioe.2024.1388907", 
         
         "author": [ 
            "Annika S. Sahrmann","Lukas Vosse","Tobias Siebert","Geoffrey G. Handsfield","Oliver Röhrle"
         ],
         "authors": [
         	
            	{"first" : "Annika S.",	"last" : "Sahrmann"},
            	{"first" : "Lukas",	"last" : "Vosse"},
            	{"first" : "Tobias",	"last" : "Siebert"},
            	{"first" : "Geoffrey G.",	"last" : "Handsfield"},
            	{"first" : "Oliver",	"last" : "Röhrle"}
         ],
         "volume": "12",
         "issn" : "2296-4185",
         
         "doi" : "10.3389/fbioe.2024.1388907",
         
         "bibtexKey": "Sahrmann2024c"

      }
,
      {
         "type" : "Publication",
         "id"   : "https://puma.ub.uni-stuttgart.de/bibtex/283fba02b010557af3f547c378cdb6de6/testusersimtech",         
         "tags" : [
            "EXC2075","PN2","PN2-8Siebert","selected"
         ],
         
         "intraHash" : "83fba02b010557af3f547c378cdb6de6",
         "interHash" : "2d12b002242e8974ec406082ad65e8b3",
         "label" : "Endomysium determines active and passive force production in muscle fibers",
         "user" : "testusersimtech",
         "description" : "",
         "date" : "2024-08-09 07:49:09",
         "changeDate" : "2024-08-09 07:49:09",
         "count" : 8,
         "pub-type": "article",
         "journal": "Journal of Biomechanics","publisher":"Elsevier BV",
         "year": "2024", 
         "url": "http://dx.doi.org/10.1016/j.jbiomech.2024.112134", 
         
         "author": [ 
            "Paolo Carlo Danesini","Maximilian Heim","André Tomalka","Tobias Siebert","Filiz Ates"
         ],
         "authors": [
         	
            	{"first" : "Paolo",	"last" : "Carlo Danesini"},
            	{"first" : "Maximilian",	"last" : "Heim"},
            	{"first" : "André",	"last" : "Tomalka"},
            	{"first" : "Tobias",	"last" : "Siebert"},
            	{"first" : "Filiz",	"last" : "Ates"}
         ],
         
         "editor": [ 
            "Tobias Siebert"
         ],
         "editors": [
         	
            	{"first" : "Tobias",	"last" : "Siebert"}
         ],
         "volume": "168","pages": "112134","abstract": "Connective tissues can be recognized as an important structural support element in muscles. Recent studies have also highlighted its importance in active force generation and transmission between muscles, particularly through the epimysium. In the present study, we aimed to investigate the impact of the endomysium, the connective tissue surrounding muscle fibers, on both passive and active force production. Pairs of skeletal muscle fibers were extracted from the extensor digitorum longus muscles of rats and, after chemical skinning, their passive and active force\u2013length relationships were measured under two conditions: (i) with the endomysium between muscle fibers intact, and (ii) after its dissection. We found that the dissection of the endomysium caused force to significantly decrease in both active (by 22.2 % when normalized to the maximum isometric force; p < 0.001) and passive conditions (by 25.9 % when normalized to the maximum isometric force; p = 0.034). These findings indicate that the absence of endomysium compromises muscle fiber\u2019s not only passive but also active force production. This effect may be attributed to increased heterogeneity in sarcomere lengths, enhanced lattice spacing between myofilaments, or a diminished role of trans-sarcolemmal proteins due to dissecting the endomysium. Future investigations into the underlying mechanisms and their implications for various extracellular matrix-related diseases are warranted.",
         "language" : "English",
         
         "issn" : "0021-9290",
         
         "doi" : "10.1016/j.jbiomech.2024.112134",
         
         "bibtexKey": "Carlo_Danesini_2024"

      }
,
      {
         "type" : "Publication",
         "id"   : "https://puma.ub.uni-stuttgart.de/bibtex/29fc3cfecc2c39e52b98d0b7689d90927/testusersimtech",         
         "tags" : [
            "EXC2075","PN2","PN2-8Siebert","selected"
         ],
         
         "intraHash" : "9fc3cfecc2c39e52b98d0b7689d90927",
         "interHash" : "c80ddfcaf1910d1f46a38466df87a8f6",
         "label" : "Reference measures of lower-limb joint range of motion, muscle strength, and selective voluntary motor control of typically developing children aged 5\u201317 years",
         "user" : "testusersimtech",
         "description" : "",
         "date" : "2024-08-09 07:49:09",
         "changeDate" : "2024-08-09 07:49:09",
         "count" : 6,
         "pub-type": "article",
         "journal": "Journal of Children\u2019s Orthopaedics","publisher":"SAGE Publications",
         "year": "2024", 
         "url": "http://dx.doi.org/10.1177/18632521241234768", 
         
         "author": [ 
            "Emily Scherff","Sabrina Elisabeth Schnell","Tobias Siebert","Sonia D\u2019Souza"
         ],
         "authors": [
         	
            	{"first" : "Emily",	"last" : "Scherff"},
            	{"first" : "Sabrina Elisabeth",	"last" : "Schnell"},
            	{"first" : "Tobias",	"last" : "Siebert"},
            	{"first" : "Sonia",	"last" : "D\u2019Souza"}
         ],
         
         "editor": [ 
            "Tobias Siebert"
         ],
         "editors": [
         	
            	{"first" : "Tobias",	"last" : "Siebert"}
         ],
         "pages": "1-10","abstract": "Background:\nJoint range of motion based on the neutral null method, muscle strength based on manual muscle testing, and selective voluntary motor control based on selective control assessment of the lower extremity are standard parameters of a pediatric three-dimensional clinical gait analysis. Lower-limb reference data of children are necessary to identify and quantify abnormalities, but these are limited and when present restricted to specific joints or muscles.\nMethods:\nThis is the first study that encompasses the aforementioned parameters from a single group of 34 typically developing children aged 5\u201317\u2009years. Left and right values were averaged for each participant, and then the mean and standard deviation calculated for the entire sample. The data set was tested for statistical significance (p\u2009<\u20090.05).\nResults:\nJoint angle reference values are mostly consistent with previously published standards, although there is a large variability in the existing literature. All muscle strength distributions, except for M. quadriceps femoris, differ significantly from the maximum value of 5. The mean number of repetitions of heel-rise test is 12\u2009±\u20095. Selective voluntary motor control shows that all distributions, except for M. quadriceps femoris, differ significantly from the maximum value of 2.\nConclusion:\nSince typically developing children do not match expectations and reference values from the available literature and clinical use, this study emphasizes the importance of normative data. Excessively high expectations lead to typically developing children being falsely underestimated and affected children being rated too low. This is of great relevance for therapists and clinicians.",
         "language" : "English",
         
         "issn" : "1863-2548",
         
         "doi" : "10.1177/18632521241234768",
         
         "bibtexKey": "Scherff_2024"

      }
,
      {
         "type" : "Publication",
         "id"   : "https://puma.ub.uni-stuttgart.de/bibtex/28da203b6974ed564e652588fd606d8e6/testusersimtech",         
         "tags" : [
            "EXC2075","PN2","PN2-5","slected"
         ],
         
         "intraHash" : "8da203b6974ed564e652588fd606d8e6",
         "interHash" : "5cfde6ff2e0d4779533cad5bb4465b95",
         "label" : "The T1150A cancer mutant of the protein lysine dimethyltransferase NSD2 can introduce H3K36 trimethylation",
         "user" : "testusersimtech",
         "description" : "",
         "date" : "2024-08-09 07:49:09",
         "changeDate" : "2024-08-09 07:49:09",
         "count" : 10,
         "pub-type": "article",
         "journal": "Journal of Biological Chemistry",
         "year": "2023", 
         "url": "https://www.sciencedirect.com/science/article/pii/S0021925823018240", 
         
         "author": [ 
            "Mina S. Khella","Philipp Schnee","Sara Weirich","Tan Bui","Alexander Bröhm","Pavel Bashtrykov","Jürgen Pleiss","Albert Jeltsch"
         ],
         "authors": [
         	
            	{"first" : "Mina S.",	"last" : "Khella"},
            	{"first" : "Philipp",	"last" : "Schnee"},
            	{"first" : "Sara",	"last" : "Weirich"},
            	{"first" : "Tan",	"last" : "Bui"},
            	{"first" : "Alexander",	"last" : "Bröhm"},
            	{"first" : "Pavel",	"last" : "Bashtrykov"},
            	{"first" : "Jürgen",	"last" : "Pleiss"},
            	{"first" : "Albert",	"last" : "Jeltsch"}
         ],
         "volume": "299","number": "6","pages": "104796--","abstract": "Protein lysine methyltransferases (PKMTs) play essential roles in gene expression regulation and cancer development. Somatic mutations in PKMTs are frequently observed in cancer cells. In biochemical experiments, we show here that the NSD1 mutations Y1971C, R2017Q, and R2017L observed mostly in solid cancers are catalytically inactive suggesting that NSD1 acts as a tumor suppressor gene in these tumors. In contrast, the frequently observed T1150A in NSD2 and its T2029A counterpart in NSD1, both observed in leukemia, are hyperactive and introduce up to three methyl groups in H3K36 in biochemical and cellular assays, while wildtype NSD2 and NSD1 only introduce up to two methyl groups. In Molecular Dynamics simulations, we determined key mechanistic and structural features controlling the product specificity of this class of enzymes. Simulations with NSD2 revealed that H3K36me3 formation is possible due to an enlarged active site pocket of T1150A and loss of direct contacts of T1150 to critical residues which regulate the product specificity of NSD2. Bioinformatic analyses of published data suggested that the generation of H3K36me3 by NSD2 T1150A could alter gene regulation by antagonizing H3K27me3 finally leading to the upregulation of oncogenes.",
         "orcid" : "0000-0003-1045-8202",
         
         "issn" : "00219258",
         
         "doi" : "https://doi.org/10.1016/j.jbc.2023.104796",
         
         "bibtexKey": "khella2023t1150a"

      }
,
      {
         "type" : "Publication",
         "id"   : "https://puma.ub.uni-stuttgart.de/bibtex/2e33a0c00c8bca389b6ef2a2dab1fa998/testusersimtech",         
         "tags" : [
            "EXC2075","PN2","misc"
         ],
         
         "intraHash" : "e33a0c00c8bca389b6ef2a2dab1fa998",
         "interHash" : "f87d2c872f2e6f474113b724ada23083",
         "label" : "A benchmark of muscle models to length changes great and small",
         "user" : "testusersimtech",
         "description" : "under review at the Journal of the Mechanical Behavior of Biomedical Materials  (JMBBM-D-24-01410)",
         "date" : "2024-08-09 07:49:09",
         "changeDate" : "2024-08-09 07:49:09",
         "count" : 16,
         "pub-type": "article",
         "journal": "bioRxiv","publisher":"Cold Spring Harbor Laboratory",
         "year": "2024", 
         "url": "https://www.biorxiv.org/content/early/2024/07/26/2024.07.26.605117", 
         
         "author": [ 
            "Matthew Millard","Norman Stutzig","Jörg Fehr","Tobias Siebert"
         ],
         "authors": [
         	
            	{"first" : "Matthew",	"last" : "Millard"},
            	{"first" : "Norman",	"last" : "Stutzig"},
            	{"first" : "Jörg",	"last" : "Fehr"},
            	{"first" : "Tobias",	"last" : "Siebert"}
         ],
         "abstract": "Digital human body models are used to simulate injuries that occur as a result of vehicle collisions, vibration, sports, and falls. Given enough time the body\u2019s musculature can generate force, affect the body\u2019s movements, and change the risk of some injuries. The finite-element code LS-DYNA is often used to simulate the movements and injuries sustained by the digital human body models as a result of an accident. In this work, we evaluate the accuracy of the three muscle models in LS-DYNA (MAT_156, EHTMM, and the VEXAT) when simulating a range of experiments performed on isolated muscle: force-length-velocity experiments on maximally and sub-maximally stimulated muscle, active-lengthening experiments, and vibration experiments. The force-length-velocity experiments are included because these conditions are typical of the muscle activity that precedes an accident, while the active-lengthening and vibration experiments mimic conditions that can cause injury. The three models perform similarly during the maximally and sub-maximally activated force-length-velocity experiments, but noticeably differ in response to the active-lengthening and vibration experiments. The VEXAT model is able to generate the enhanced forces of biological muscle during active lengthening, while both the MAT_156 and EHTMM produce too little force. In response to vibration, the stiffness and damping of the VEXAT model closely follows the experimental data while the MAT_156 and EHTMM models differ substantially. The accuracy of the VEXAT model comes from two additional mechanical structures that are missing in the MAT_156 and EHTMM models: viscoelastic cross-bridges, and an active titin filament. To help others build on our work we have made our benchmark simulations and model code publicly available.Competing Interest StatementThe authors have declared no competing interest.",
         "elocation-id" : "2024.07.26.605117",
         
         "eprint" : "https://www.biorxiv.org/content/early/2024/07/26/2024.07.26.605117.full.pdf",
         
         "doi" : "10.1101/2024.07.26.605117",
         
         "bibtexKey": "Millard2024.07.26.605117"

      }
,
      {
         "type" : "Publication",
         "id"   : "https://puma.ub.uni-stuttgart.de/bibtex/2c238b758cffde09f65b3a94638a40594/testusersimtech",         
         "tags" : [
            "EXC2075","PN2","misc"
         ],
         
         "intraHash" : "c238b758cffde09f65b3a94638a40594",
         "interHash" : "f16bfe6c9d372ee32c3cd78f5201f549",
         "label" : "Potential to Volunteer Testing Using a Driving Simulator with Motion Capture and EMG Data Acquisition",
         "user" : "testusersimtech",
         "description" : "",
         "date" : "2024-08-09 07:49:09",
         "changeDate" : "2024-08-09 07:49:09",
         "count" : 6,
         "pub-type": "inproceedings",
         "booktitle": "Proceedings of the IRCOBI Conference","address":"Munich, Germany",
         "year": "2021", 
         "url": "http://www.ircobi.org/wordpress/downloads/irc21/pdf-files/2175.pdf", 
         
         "author": [ 
            "F. Kempter","L. Lantella","N. Stutzig","J. Fehr","T. Siebert"
         ],
         "authors": [
         	
            	{"first" : "F.",	"last" : "Kempter"},
            	{"first" : "L.",	"last" : "Lantella"},
            	{"first" : "N.",	"last" : "Stutzig"},
            	{"first" : "J.",	"last" : "Fehr"},
            	{"first" : "T.",	"last" : "Siebert"}
         ],
         "number": "IRC-21-75",
         "owner" : "fkempter",
         
         "file" : "KempterEtAl21.pdf:KempterEtAl21.pdf:PDF",
         
         "bibtexKey": "kempter2021potential"

      }
,
      {
         "type" : "Publication",
         "id"   : "https://puma.ub.uni-stuttgart.de/bibtex/23aedd0115f2b9e0b650716ad487f39d1/testusersimtech",         
         "tags" : [
            "EXC2075","PN2","PNX","curated","misc"
         ],
         
         "intraHash" : "3aedd0115f2b9e0b650716ad487f39d1",
         "interHash" : "fa256e8a795c7d220fbe2b965dc7ea6c",
         "label" : "A three filament mechanistic model of musculotendon force and impedance",
         "user" : "testusersimtech",
         "description" : "",
         "date" : "2024-08-09 07:49:09",
         "changeDate" : "2024-08-09 07:49:09",
         "count" : 5,
         "pub-type": "article",
         "journal": "eLife Computational and Systems Biologiy","publisher":"eLife Sciences Publications, Ltd",
         "year": "2024", 
         "url": "", 
         
         "author": [ 
            "Matthew Millard","David W Franklin","Walter Herzog"
         ],
         "authors": [
         	
            	{"first" : "Matthew",	"last" : "Millard"},
            	{"first" : "David W",	"last" : "Franklin"},
            	{"first" : "Walter",	"last" : "Herzog"}
         ],
         "note": "accepted for publication","abstract": "The force developed by actively lengthened muscle depends on different structures across different scales of lengthening. For small perturbations, the active response of muscle is well captured by a linear-time-invariant (LTI) system: a stiff spring in parallel with a light damper. The force response of muscle to longer stretches is better represented by a compliant spring that can fix its end when activated. Experimental work has shown that the stiffness and damping (impedance) of muscle in response to small perturbations is of fundamental importance to motor learning and mechanical stability, while the huge forces developed during long active stretches are critical for simulating and predicting injury. Outside of motor learning and injury, muscle is actively lengthened as a part of nearly all terrestrial locomotion. Despite the functional importance of impedance and active lengthening, no single muscle model has all of these mechanical properties. In this work, we present the viscoelastic-crossbridge active-titin (VEXAT) model that can replicate the response of muscle to length changes great and small. To evaluate the VEXAT model, we compare its response to biological muscle by simulating experiments that measure the impedance of muscle, and the forces developed during long active stretches. In addition, we have also compared the responses of the VEXAT model to a popular Hill-type muscle model. The VEXAT model more accurately captures the impedance of biological muscle and its responses to long active stretches than a Hill-type model and can still reproduce the force-velocity and force-length relations of muscle. While the comparison between the VEXAT model and biological muscle is favorable, there are some phenomena that can be improved: the low frequency phase response of the model, and a mechanism to support passive force enhancement.Competing Interest StatementThe authors have declared no competing interest.",
         "elocation-id" : "2023.03.27.534347",
         
         "eprint" : "https://www.biorxiv.org/content/early/2023/11/27/2023.03.27.534347.full.pdf",
         
         "preprinturl" : "https://www.biorxiv.org/content/early/2023/11/27/2023.03.27.534347",
         
         "doi" : "https://doi.org/10.7554/eLife.88344.3",
         
         "bibtexKey": "millard2023three"

      }
,
      {
         "type" : "Publication",
         "id"   : "https://puma.ub.uni-stuttgart.de/bibtex/20cbfb38c667ce84ea8ce418a1d3dafea/testusersimtech",         
         "tags" : [
            "EXC2075","PN2","PN2-6","selected"
         ],
         
         "intraHash" : "0cbfb38c667ce84ea8ce418a1d3dafea",
         "interHash" : "77462f05df223eb8b5d4ca12ed48de1b",
         "label" : "FAIR Data and Software: Improving Efficiency and Quality of Biocatalytic Science",
         "user" : "testusersimtech",
         "description" : "",
         "date" : "2024-07-19 15:07:18",
         "changeDate" : "2024-07-19 15:07:18",
         "count" : 6,
         "pub-type": "article",
         "journal": "ACS Catal.","booktitle": "ACS Catalysis","publisher":"American Chemical Society",
         "year": "2024", 
         "url": "https://doi.org/10.1021/acscatal.3c06337", 
         
         "author": [ 
            "Jürgen Pleiss"
         ],
         "authors": [
         	
            	{"first" : "Jürgen",	"last" : "Pleiss"}
         ],
         "volume": "14","number": "4","pages": "2709--2718",
         "orcid" : "0000-0003-1045-8202",
         
         "comment" : "doi: 10.1021/acscatal.3c06337",
         
         "doi" : "10.1021/acscatal.3c06337",
         
         "bibtexKey": "pleiss2024software"

      }
,
      {
         "type" : "Publication",
         "id"   : "https://puma.ub.uni-stuttgart.de/bibtex/2779a4a47514c9889402e09ddb7d4802b/testusersimtech",         
         "tags" : [
            "EXC2075","PN2","PN2-6","PN2-6(II)","selected"
         ],
         
         "intraHash" : "779a4a47514c9889402e09ddb7d4802b",
         "interHash" : "3aa0a31660b9738217832524450abb82",
         "label" : "MetaConfigurator: A User-Friendly Tool for Editing Structured Data Files",
         "user" : "testusersimtech",
         "description" : "",
         "date" : "2024-07-19 15:07:18",
         "changeDate" : "2024-07-19 15:07:18",
         "count" : 6,
         "pub-type": "article",
         "journal": "Datenbank-Spektrum",
         "year": "2024", 
         "url": "https://doi.org/10.1007/s13222-024-00472-7", 
         
         "author": [ 
            "Felix Neubauer","Paul Bredl","Minye Xu","Keyuriben Patel","Jürgen Pleiss","Benjamin Uekermann"
         ],
         "authors": [
         	
            	{"first" : "Felix",	"last" : "Neubauer"},
            	{"first" : "Paul",	"last" : "Bredl"},
            	{"first" : "Minye",	"last" : "Xu"},
            	{"first" : "Keyuriben",	"last" : "Patel"},
            	{"first" : "Jürgen",	"last" : "Pleiss"},
            	{"first" : "Benjamin",	"last" : "Uekermann"}
         ],
         "volume": "24","pages": "161\u2013169","abstract": "Textual formats to structure data, such as JSON, XML, and YAML, are widely used for structuring data in various domains, from configuration files to research data. However, manually editing data in these formats can be complex and time-consuming. Graphical user interfaces (GUIs) can significantly reduce manual efforts and assist the user in editing the files, but developing a file-format-specific GUI requires substantial development and maintenance efforts. To address this challenge, we introduce MetaConfigurator: an open-source web application that generates its GUI depending on a given schema. Our approach differs from other schema-to-UI approaches in three key ways: 1) It offers a unified view that combines the benefits of both GUIs and text editors, 2) it enables schema editing within the same tool, and 3) it supports advanced schema features, including conditions and constraints. In this paper, we discuss the design and implementation of MetaConfigurator, backed by insights from a small-scale qualitative user study. The results indicate the effectiveness of our approach in retrieving information from data and schemas and in editing them.",
         "orcid" : "0000-0003-1045-8202",
         
         "issn" : "16101995",
         
         "refid" : "Neubauer2024",
         
         "doi" : "10.1007/s13222-024-00472-7",
         
         "bibtexKey": "neubauer2024metaconfigurator"

      }
,
      {
         "type" : "Publication",
         "id"   : "https://puma.ub.uni-stuttgart.de/bibtex/272af99c797370695f57647c06fb10429/testusersimtech",         
         "tags" : [
            "EXC2075","PN2","PN2-5","selected"
         ],
         
         "intraHash" : "72af99c797370695f57647c06fb10429",
         "interHash" : "08a87a4b59f0eec9105c21ec6be71ee4",
         "label" : "Discovery of NSD2 non-histone substrates and design of a super-substrate",
         "user" : "testusersimtech",
         "description" : "",
         "date" : "2024-07-19 15:07:18",
         "changeDate" : "2024-07-19 15:07:18",
         "count" : 7,
         "pub-type": "article",
         "journal": "Communications Biology",
         "year": "2024", 
         "url": "https://doi.org/10.1038/s42003-024-06395-z", 
         
         "author": [ 
            "Sara Weirich","Denis Kusevic","Philipp Schnee","Jessica Reiter","Jürgen Pleiss","Albert Jeltsch"
         ],
         "authors": [
         	
            	{"first" : "Sara",	"last" : "Weirich"},
            	{"first" : "Denis",	"last" : "Kusevic"},
            	{"first" : "Philipp",	"last" : "Schnee"},
            	{"first" : "Jessica",	"last" : "Reiter"},
            	{"first" : "Jürgen",	"last" : "Pleiss"},
            	{"first" : "Albert",	"last" : "Jeltsch"}
         ],
         "volume": "7","number": "1","pages": "707--","abstract": "The human protein lysine methyltransferase NSD2 catalyzes dimethylation at H3K36. It has very important roles in development and disease but many mechanistic features and its full spectrum of substrate proteins are unclear. Using peptide SPOT array methylation assays, we investigate the substrate sequence specificity of NSD2 and discover strong readout of residues between G33 (-3) and P38 (+2) on H3K36. Unexpectedly, we observe that amino acid residues different from natural ones in H3K36 are preferred at some positions. Combining four preferred residues led to the development of a super-substrate which is methylated much faster by NSD2 at peptide and protein level. Molecular dynamics simulations demonstrate that this activity increase is caused by distinct hyperactive conformations of the enzyme-peptide complex. To investigate the substrate spectrum of NSD2, we conducted a proteome wide search for nuclear proteins matching the specificity profile and discovered 22 peptide substrates of NSD2. In protein methylation studies, we identify K1033 of ATRX and K819 of FANCM as NSD2 methylation sites and also demonstrate their methylation in human cells. Both these proteins have important roles in DNA repair strengthening the connection of NSD2 and H3K36 methylation to DNA repair.",
         "orcid" : "0000-0003-1045-8202",
         
         "issn" : "23993642",
         
         "refid" : "Weirich2024",
         
         "doi" : "10.1038/s42003-024-06395-z",
         
         "bibtexKey": "weirich2024discovery"

      }
,
      {
         "type" : "Publication",
         "id"   : "https://puma.ub.uni-stuttgart.de/bibtex/2090e8f7d3529477f0ee5f4494ab990f7/testusersimtech",         
         "tags" : [
            "EXC2075","PN2","PN2-5","selected"
         ],
         
         "intraHash" : "090e8f7d3529477f0ee5f4494ab990f7",
         "interHash" : "7ca7381ffe7ca141c4443fe59a462873",
         "label" : "Mechanistic basis of the increased methylation activity of the SETD2 protein lysine methyltransferase towards a designed super-substrate peptide",
         "user" : "testusersimtech",
         "description" : "",
         "date" : "2024-07-19 15:07:18",
         "changeDate" : "2024-07-19 15:07:18",
         "count" : 9,
         "pub-type": "article",
         "journal": "Communications Chemistry",
         "year": "2022", 
         "url": "https://doi.org/10.1038/s42004-022-00753-w", 
         
         "author": [ 
            "Philipp Schnee","Michel Choudalakis","Sara Weirich","Mina S. Khella","Henrique Carvalho","Jürgen Pleiss","Albert Jeltsch"
         ],
         "authors": [
         	
            	{"first" : "Philipp",	"last" : "Schnee"},
            	{"first" : "Michel",	"last" : "Choudalakis"},
            	{"first" : "Sara",	"last" : "Weirich"},
            	{"first" : "Mina S.",	"last" : "Khella"},
            	{"first" : "Henrique",	"last" : "Carvalho"},
            	{"first" : "Jürgen",	"last" : "Pleiss"},
            	{"first" : "Albert",	"last" : "Jeltsch"}
         ],
         "volume": "5","number": "1","pages": "139--","abstract": "Protein lysine methyltransferases have important regulatory functions in cells, but mechanisms determining their activity and specificity are incompletely understood. Naturally, SETD2 introduces H3K36me3, but previously an artificial super-substrate (ssK36) was identified, which is methylated >100-fold faster. The ssK36-SETD2 complex structure cannot fully explain this effect. We applied molecular dynamics (MD) simulations and biochemical experiments to unravel the mechanistic basis of the increased methylation of ssK36, considering peptide conformations in solution, association of peptide and enzyme, and formation of transition-state (TS) like conformations of the enzyme-peptide complex. We observed in MD and FRET experiments that ssK36 adopts a hairpin conformation in solution with V35 and K36 placed in the loop. The hairpin conformation has easier access into the active site of SETD2 and it unfolds during the association process. Peptide methylation experiments revealed that introducing a stable hairpin conformation in the H3K36 peptide increased its methylation by SETD2. In MD simulations of enzyme-peptide complexes, the ssK36 peptide approached TS-like structures more frequently than H3K36 and distinct, substrate-specific TS-like structures were observed. Hairpin association, hairpin unfolding during association, and substrate-specific catalytically competent conformations may also be relevant for other PKMTs and hairpins could represent a promising starting point for SETD2 inhibitor development.",
         "orcid" : "0000-0003-1045-8202",
         
         "issn" : "23993669",
         
         "refid" : "Schnee2022",
         
         "doi" : "10.1038/s42004-022-00753-w",
         
         "bibtexKey": "schnee2022mechanistic"

      }
	  
   ]
}
