Analysis of domain motions by approximate normal mode calculations

TLDR

Identifying dynamical domains and describing low‑frequency domain motions is a key application of numerical simulation techniques, yet applying these methods to large proteins is computationally demanding and often impractical. This article demonstrates that physically motivated approximations enable calculation of low‑frequency normal modes in only a few minutes on standard desktop computers. The approach relies on the observation that low‑frequency modes, which capture domain motions, are largely independent of force‑field details and can be derived from simplified mechanical models that also quantify protein rigidity and identify quasi‑rigid domains. The method was validated on the proteins crambin, lysozyme, and ATCase, confirming its effectiveness and providing new insights into the relevance of normal‑mode analysis and the underlying potential‑energy surface. Proteins 33:417–429, 1998.

Abstract

The identification of dynamical domains in proteins and the description of the low-frequency domain motions are one of the important applications of numerical simulation techniques. The application of these techniques to large proteins requires a substantial computational effort and therefore cannot be performed routinely, if at all. This article shows how physically motivated approximations permit the calculation of low-frequency normal modes in a few minutes on standard desktop computers. The technique is based on the observation that the low-frequency modes, which describe domain motions, are independent of force field details and can be obtained with simplified mechanical models. These models also provide a useful measure for rigidity in proteins, allowing the identification of quasi-rigid domains. The methods are validated by application to three well-studied proteins, crambin, lysozyme, and ATCase. In addition to being useful techniques for studying domain motions, the success of the approximations provides new insight into the relevance of normal mode calculations and the nature of the potential energy surface of proteins. Proteins 33:417–429, 1998. © 1998 Wiley-Liss, Inc.