The Simbios National Center for Biomedical Computing is singularly focused on the application of physics-based simulation to problems in biology and medicine. Physics-based simulation provides a powerful framework for understanding biological form and function. Simulations are used by biologists to study macromolecular assemblies and by clinicians to analyze disease mechanisms and therapeutic options. Simulations help biomedical researchers understand the physical constraints on these systems as they engineer novel drugs, drug delivery mechanisms, synthetic tissues, medical devices, or surgical interventions. In the previous grant period, we have created a simulation toolkit (SimTK) that enables users to create and visualize accurate models and simulations of biological structures at all scales, from molecules to organisms. SimTK is an extensible, open source, freely available software package. Domain specific application software packages (built using SimTK) are distributed on our webportal,, which has more than 8000 users and 300 software or data projects, and has enabled scientific impact in RNA biology, myosin biomechanics, protein folding, cardiovascular fluid dynamics, and neuromuscular biomechanics. SimTK applications have been developed and tested in close collaboration with biomedical scientists to ensure its utility and accuracy. In this proposal, we outline a plan to introduce three exciting new driving biological problems focusing on (1) the dynamics of neural prostheses, (2) the dynamics of cell shape, and (3) the dynamics of drug target macromolecules. We have identified the computational research challenges critical to these fields, and have assembled a strong team of researchers in modeling, simulation and visualization of biological structures that will address these challenges. The software engineering effort is lead by experienced professionals, who have previously developed and delivered complex software packages to thousands of users. Our dissemination plan includes workshops that will move online, a nationally recognized magazine, and technologies for community-based user support. Our initial efforts have established the vision, facilities, training environment, administrative organization, and collaborative relationships required for the success of Simbios. In the context of other centers focusing on complementary elements of biomedicine, our center is focused on the physical reality of biological structures. It thus provides a critical piece of a national biomedical computing infrastructure.

Public Health Relevance

Physical simulation of cars, airplanes, and all manner of physical devices is routine in their design and analysis, but biomedical systems are more complex than these mechanical systems, and our ability to simulate their structure and motion has been limited. In this proposal, we outline a plan for a National Center of Biomedical Computation entirely devoted to physics-based simulation of biological structures (Simbios). We will build simulation software (and make it publicly available for routine use) that will help us design new drugs, understand infectious processes of bacteria, and provide brain control of prosthetic limbs.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BST-K (52))
Program Officer
Lyster, Peter
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
DeMers, Matthew S; Hicks, Jennifer L; Delp, Scott L (2017) Preparatory co-activation of the ankle muscles may prevent ankle inversion injuries. J Biomech 52:17-23
Sack, Kevin L; Baillargeon, Brian; Acevedo-Bolton, Gabriel et al. (2016) Partial LVAD restores ventricular outputs and normalizes LV but not RV stress distributions in the acutely failing heart in silico. Int J Artif Organs 39:421-430
Shukla, Diwakar; Peck, Ariana; Pande, Vijay S (2016) Conformational heterogeneity of the calmodulin binding interface. Nat Commun 7:10910
Araya, Carlos L; Cenik, Can; Reuter, Jason A et al. (2016) Identification of significantly mutated regions across cancer types highlights a rich landscape of functional molecular alterations. Nat Genet 48:117-25
Dodani, Sheel C; Kiss, Gert; Cahn, Jackson K B et al. (2016) Discovery of a regioselectivity switch in nitrating P450s guided by molecular dynamics simulations and Markov models. Nat Chem 8:419-25
Meng, Yilin; Shukla, Diwakar; Pande, Vijay S et al. (2016) Transition path theory analysis of c-Src kinase activation. Proc Natl Acad Sci U S A 113:9193-8
Sahli Costabal, Francisco; Hurtado, Daniel E; Kuhl, Ellen (2016) Generating Purkinje networks in the human heart. J Biomech 49:2455-65
Uchida, Thomas K; Hicks, Jennifer L; Dembia, Christopher L et al. (2016) Stretching Your Energetic Budget: How Tendon Compliance Affects the Metabolic Cost of Running. PLoS One 11:e0150378
Schwantes, Christian R; Shukla, Diwakar; Pande, Vijay S (2016) Markov State Models and tICA Reveal a Nonnative Folding Nucleus in Simulations of NuG2. Biophys J 110:1716-1719
Seth, Ajay; Matias, Ricardo; Veloso, António P et al. (2016) A Biomechanical Model of the Scapulothoracic Joint to Accurately Capture Scapular Kinematics during Shoulder Movements. PLoS One 11:e0141028

Showing the most recent 10 out of 249 publications