A Heirarchical framework for constrained molecular dynamics method

Molecular dynamics (MD) simulation is a powerful computational tool in structural biology, widely used for understanding conformational changes in proteins, and folding of peptides. However MD simulations using Cartesian dynamics model is limited by the total simulation time scale being in tens of nanoseconds for large proteins. Biological processes on the other hand need microseconds of simulation time. We developed the Internal Coordinate Molecular Dynamics (ICMD) algorithms in the early 1990s to enable larger simulation time-steps and they show great promise in long time scale simulations. Despite their promise, ICMD techniques have made little progress due in large part to the additional mathematical complexity of internal coordinate models. As a NIH-NIGMS project and in collaboration with Dr. Abhi Jain at the NASA Jet Propulsion Laboratory at Caltech, we are developing the ICMD methods called Generalized Newton-Euler Inverse Mass Operator (GNEIMO) to enable long time scale and wider conformational search simulations. These simulations have been tested to fold simple proteins from extended structure and we are in the process of extending this method to study large scale conformational changes in proteins.

Publications related to this project:

• Jain A, Vaidehi N, Rodriguez G A 1993, Fast Recursive Algorithm For Molecular-Dynamics Simulation, J Comput Phys 106: (2) 258-268.Vaidehi N., Jain A., Goddard III, W.A., 1996, Constant temperature constrained molecular dynamics: The Newton-Euler inverse mass operator method, J Phys Chem-100: (25) 10508-10517.
• Bertsch R.A., Vaidehi  N., Chan S.I., et al. 1998,  Kinetic steps for alpha-helix formation Proteins: Structure, Function and Genetics, 33: (3) 343-357.
• Vaidehi N., Goddard W.A., 2000, Domain motions in phosphoglycerate kinase using hierarchical NEIMO molecular dynamics simulations,  J Phys. Chem.  A 104: (11) 2375-2383.
• Balaraman, G., Park I., Jain A., and Vaidehi N., 2011, Folding of Small Proteins Using Constrained Molecular Dynamics, J. Phys. Chem B in press.