Can conformational change be described by only a few normal modes?

¹ Stanford
² Stanford University

^* To whom correspondence should be addressed. E-mail: pande{at}stanford.edu.

Submitted on July 5, 2005
Revised on August 18, 2005
Accepted on 28 November 2005

	Abstract

We suggest a simple method to assess how many normal modes are needed to map a conformational change. By projecting the conformational change onto a subspace of the normal mode vectors and, using RMSD as a test of accuracy, we find that the first 20 modes only contribute 50% or less of the total conformational change in four test cases (myosin, calmodulin, NtrC, and hemoglobin). In some allosteric systems, like the molecular switch NtrC, the conformational change is localized to a limited number of residues. We find that many more modes are necessary to accurately map this collective displacement. In addition, the normal mode "spectra" can provide useful information about the details of the conformational change, especially when comparing structures with different bound ligands, in this case, calmodulin. Indeed, this approach presents normal mode analysis as a useful basis in which to capture the mechanism of conformational change, and shows that the number of normal modes needed to capture the essential collective motions of atoms should be chosen according to the required accuracy.

Key Words: allostery, coarse-grain, conformational change, normal-mode

This article has been cited by other articles:

				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]

				E. Eyal and I. Bahar Toward a Molecular Understanding of the Anisotropic Response of Proteins to External Forces: Insights from Elastic Network Models Biophys. J., May 1, 2008; 94(9): 3424 - 3435. [Abstract] [Full Text] [PDF]