77 / 161
Conformational Ensembles from Experimental Data
and Computer Simulations
Poster Abstracts
73
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.