Dynamics of Proteins

Abstract

INTRODUCTION / It has long been recognized that proteins are dynamic systems. Although the three-dimensional structures, which have been determined for an increasing number of proteins, provide some basic insight into the architecture of these molecules, taken alone they cannot explain the observed properties and functions in any mechanistic sense. To quote an example, Perutz & Mathews first noted that the equilibrium structure of hemoglobin leaves no room for a ligand to reach the buried heme binding site (1); the same observation applies to the 02 storage protein myoglobin (Mb), as revealed by x-ray diffraction at 2 A resolution (2). There is ample evidence that the substrate gains access to the interior of Mb as a result of the thermal motion of the polypeptide chain (3). Chain mobility is obviously essential in protein folding (4, 5), but the question that concerns us here is the dynamics of the folded, native form. Conforma­ tional transitions (6-8), allostery (9), active transport (10), enzymatic activity (6, 11), and motility (12, 13) are processes that obviously depend on internal mobility. To delineate the driving forces and pathways of protein reactions is still a distant goal (14). Much progress has been made, however, in the description of the internal dynamics of proteins. While theory makes important predictions about the fluctuations in the thermodynamic parameters of macromolecules (15), a deeper under­ standing of protein dynamics has come from experiments and model calculations (16, 17) on several globular, water soluble proteins. There is hope that the results are representative for this class of proteins, but t�e methods used do not yet provide a comprehensive picture of protein dynamics. The problem is that the characteristic frequencies of the interatomic forces have an enormously wide spectrum, from 10-13 sec to