Fluctuations and Correlations in Crystalline Protein Dynamics: A Simulation Analysis of Staphylococcal Nuclease

¹ University of Heidelberg
² Universitaet Heidelberg

^* To whom correspondence should be addressed. E-mail: lars{at}meinhold.de.

Submitted on November 10, 2004
Revised on January 6, 2005
Accepted on 25 January 2005

	Abstract

Understanding collective motions in protein crystals is likely to furnish insight into functional protein dynamics and will improve models for refinement against diffraction data. Here, four 10 ns molecular dynamics simulations of crystalline Staphylococcal Nuclease are reported and analysed in terms of fluctuations and correlations in atomic motion. The simulation-derived fluctuations strongly correlate with, but are slightly higher than, the values derived from the experimental B-factors. About 70% of the atomic fluctuations are due to internal protein motion. For 65% of the protein atoms the internal fluctuations converge on the nanosecond timescale. Convergence is much slower for the elements of the interatomic displacement correlation matrix - of these more than 80% converge within 1 ns for interatomic distances 6Å, but only 10% for separations 12Å. Those collective motions converged on the nanosecond timescale involve mostly correlations within the -barrel or between -helices of the protein. The R-factor with the experimental X-ray diffuse scattering for the crystal, which is determined by the displacement variance-covariance matrix, decreases to 8% after 10 ns simulation. Both the number of converged correlation matrix elements and the R-factor depend logarithmically on time, consistent with a model in which the number of energy minima sampled depends exponentially on the maximum energy barrier crossed. The logarithmic dependence is also extrapolated to predict a convergence time for the whole variance-covariance matrix of 1 µs.

Key Words: B-factors, X-ray diffuse scattering, convergence, correlated displacements, molecular dynamics, variance-covariance matrix

This article has been cited by other articles:

				L. Meinhold, D. Clement, M. Tehei, R. Daniel, J. L. Finney, and J. C. Smith Protein Dynamics and Stability: The Distribution of Atomic Fluctuations in Thermophilic and Mesophilic Dihydrofolate Reductase Derived Using Elastic Incoherent Neutron Scattering Biophys. J., June 15, 2008; 94(12): 4812 - 4818. [Abstract] [Full Text] [PDF]

				L. Zhou and S. A. Siegelbaum Effects of Surface Water on Protein Dynamics Studied by a Novel Coarse-Grained Normal Mode Approach Biophys. J., May 1, 2008; 94(9): 3461 - 3474. [Abstract] [Full Text] [PDF]

				P. J. Bond, J. D. Faraldo-Gomez, S. S. Deol, and M. S. P. Sansom Membrane protein dynamics and detergent interactions within a crystal: A simulation study of OmpA PNAS, June 20, 2006; 103(25): 9518 - 9523. [Abstract] [Full Text] [PDF]