Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Poster Abstracts

40-POS Board 40 Closing the Gap Between NMR Relaxation and Molecular Dynamics Simulations of Methyl Dynamics in Proteins Falk Hoffmann 1 , Mengjun Xue 2 , Lars Schäfer 1 , Frans Mulder 2 . 1 Ruhr-University Bochum, Bochum, Germany, 2 University of Aarhus, Aarhus, Denmark. Molecular dynamics (MD) simulations and nuclear magnetic resonance (NMR) spin relaxation experiments have become increasingly powerful to study protein dynamics at atomic resolution due to steady improvements in physical models and computation power. Good agreement between generalized Lipari-Szabo (S 2 NH ) order parameters derived from experiment and simulation is now observed for the backbone dynamics of a number of proteins. Unfortunately, the agreement for side chains, as e.g. probed by S 2 CH3 for methyl-containing side chains, is much poorer. In this work we discuss several issues with methyl side chains that need to be addressed to close the gap between NMR and MD. Accounting for protein tumbling is the single most important factor to obtain a good agreement. In our hands, the application of improved water force fields with an appropriate way of including anisotropic overall protein tumbling improves the prediction of experimentally measured dynamic observables by MD simulations. We demonstrate these aspects for T4 lysozyme as an example. Our results guide the way for extracting the most accurate parameters that describe protein side chain dynamics and report on conformational entropy from the NMR relaxation data.

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