Paths in the conformational space of biopolymers

Laboratoire de Physique Quantique, Université Paul-Sabatier, 118, route de Narbonne, 31062 Toulouse, France.

Abstract

This lecture will start with a survey of the present state of knowledge on the topology of potential hypersurfaces of proteins, on transitions in conformational space, and on harmonic and quasi-harmonic methods of computation of thermodynamic and kinetic quantities. The concepts of deterministics vs ergodic behaviour and of kinetic vs thermodynamic control will be discussed. More specifically, the possible connection between selectivity (or "accuracy") in enzyme catalysis and the time structure of conformational transitions will be shown, indicating the functional advantage of an unique path consisting of a sequence of transitions between substates.

In a second part, two different methods used by the authors for theoretical computation of conformational paths in citrate synthase (1) will be commented, as well as the main features of the paths obtained (2). The picture which emerges from this study is that of sinuous conformational paths with essentially constant energy. A hint on the transition time will be given.

Finally, in connection with the "multiple minima problem", the occurrence of lower and upper bounds in the temperatures used in molecular dynamics searches of conformational minima will be discussed with emphasis on their dependence with respect to the problem under consideration (structure refinement or path determination) and to the imposition of constraints on the conformational space investigated.