Application of All-Atom and Coarse-Grained Molecular Dynamics Simulations to Long Timescale Structural Transitions of Proteins
Freddolino, Peter L.
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https://hdl.handle.net/2142/72399
Description
Title
Application of All-Atom and Coarse-Grained Molecular Dynamics Simulations to Long Timescale Structural Transitions of Proteins
Author(s)
Freddolino, Peter L.
Issue Date
2009
Doctoral Committee Chair(s)
Schulten, Klaus J.
Department of Study
Center for Biophysics and Computational Biology
Discipline
Biophysics and Computational Biology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biophysics, General
Abstract
Experimental methods in biology are generally able to provide low-resolution data on specific functions of biomolecules, or high-resolution data on structures and other properties in states of questionable physiological relevance, but very rarely both at the same time. Molecular dynamics (MD) simulations, in contrast, offer data on the motion of biomolecules with very high spatial and temporal resolution, and allow easy manipulation of the biomolecules and their environment to test the effects of perturbations such as mutations. MD simulations are limited, however, both in the timescales that they can access (usually on the order of nanoseconds) and by the accuracy of MD potential energy functions and parameters. This thesis presents a series of applications of MD to systems which are generally beyond the reach of such simulations, through a combination of force (the application of supercomputing resources) and finesse (the use of coarse graining methods). The applications include all-atom simulations of the mechanism of light detection by plant phototropins, the folding process of the WW domain and villin headpiece, the assembly and stability of a variety of viral capsids, the assembly and disassembly of high density lipoprotein particles, and the rotation of the bacterial flagellum. In each case, molecular dynamics simulations provided qualitatively new insights that are in line with previous, contemporary or subsequent experiments. In addition to exploring how molecular dynamics simulations can be extended to longer time and length scales, several of the all-atom simulations suggested avenues for improvement in modern MD force fields, and the coarse graining work lead to the development of novel methods to simulate proteins using reduced representations.
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