Atomically detailed simulations of a biomolecular process can provide significant insight to mechanisms and function, and are therefore widely used. Nevertheless, enthusiasm for these simulations is somewhat reduced when we consider their time scale limitation. Time scales of Molecular Dynamics (MD) simulations are restricted to a few microseconds, significantly shorter than time scales of many processes in molecular biophysics, such as rapid and slow folding, conformational transitions and activation, and signal transduction. In the previous funding periods we focused on the calculation of approximate trajectories that describe long time (even millisecond) processes. The trajectories compared favorably with experiments on structural properties of paths. However, the calculation of kinetic properties proved difficult. Determining rate is important since kinetic of cellular processes describes function;it is also at the core of the timely field of System Biology. We developed a new computational technique, Milestoning, to calculate rates. In the next grant period we plan to advance the new methodology, and to compute the kinetics of myosin recovery stroke and allosteric transition in Scapharca hemoglobin. Our algorithms are implemented in the Molecular Dynamics package MOIL which continues to be freely available at

Public Health Relevance

to Public Health The algorithm developed in the grant will help predict kinetics (and function) of proteins and are likely to give better understanding of proteins and their interactions with other molecules (like drugs).

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Macromolecular Structure and Function B Study Section (MSFB)
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Preusch, Peter C
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University of Texas Austin
Engineering (All Types)
Schools of Engineering
United States
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Chen, Szu-Hua; Elber, Ron (2014) The energy landscape of a protein switch. Phys Chem Chem Phys 16:6407-21
Viswanath, Shruthi; Ravikant, D V S; Elber, Ron (2014) DOCK/PIERR: web server for structure prediction of protein-protein complexes. Methods Mol Biol 1137:199-207
Michele, Di Pierro; Ron, Elber (2013) Automated Optimization of Potential Parameters. J Chem Theory Comput 9:3311-3320
Viswanath, Shruthi; Kreuzer, Steven M; Cardenas, Alfredo E et al. (2013) Analyzing milestoning networks for molecular kinetics: definitions, algorithms, and examples. J Chem Phys 139:174105
Kreuzer, Steven M; Elber, Ron; Moon, Tess J (2012) Early events in helix unfolding under external forces: a milestoning analysis. J Phys Chem B 116:8662-91
Kirmizialtin, Serdal; Nguyen, Virginia; Johnson, Kenneth A et al. (2012) How conformational dynamics of DNA polymerase select correct substrates: experiments and simulations. Structure 20:618-27
Kirmizialtin, Serdal; Pabit, Suzette A; Meisburger, Steve P et al. (2012) RNA and its ionic cloud: solution scattering experiments and atomically detailed simulations. Biophys J 102:819-28
Cottone, Grazia; Lattanzi, Gianluca; Ciccotti, Giovanni et al. (2012) Multiphoton absorption of myoglobin-nitric oxide complex: relaxation by D-NEMD of a stationary state. J Phys Chem B 116:3397-410
Cardenas, Alfredo E; Jas, Gouri S; DeLeon, Kristine Y et al. (2012) Unassisted transport of N-acetyl-L-tryptophanamide through membrane: experiment and simulation of kinetics. J Phys Chem B 116:2739-50
Ruymgaart, A Peter; Cardenas, Alfredo E; Elber, Ron (2011) MOIL-opt: Energy-Conserving Molecular Dynamics on a GPU/CPU system. J Chem Theory Comput 7:3072-3082

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