Predicting large-scale conformational changes in proteins using energy-weighted normal modes |
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Authors: | Palmer David S Jensen Frank |
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Institution: | Department of Chemistry, Aarhus University, Aarhus C, Denmark. |
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Abstract: | We report the development of a method to improve the sampling of protein conformational space in molecular simulations. It is shown that a principal component analysis of energy-weighted normal modes in Cartesian coordinates can be used to extract vectors suitable for describing the dynamics of protein substructures. The method can operate with either atomistic or user-defined coarse-grained models of protein structure. An implicit reverse coarse-graining allows the dynamics of all-atoms to be recovered when a coarse-grained model is used. For an external test set of four proteins, it is shown that the new method is more successful than normal mode analysis in describing the large-scale conformational changes observed on ligand binding. The method has potential applications in protein-ligand and protein-protein docking and in biasing molecular dynamics simulations. |
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Keywords: | harmonic vibrational docking sampling molecular dynamics |
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