An overview on protein structure determination by NMR: Historical and future perspectives of the use of distance geometry methods

Abstract

Determination of the protein high-resolution structures is essential for the understanding of complex biological mechanisms, for the development of biotechnological methods, and for other applications such as drug discovery. Protein structures solved by nuclear magnetic resonance (NMR) rely on a set of semiquantitative short-range distances and angles information. The exploration of the whole conformational space imposed by the experimental restraints is not a computationally simple problem. The lack of precise distances and angles does not allow to find solutions to this problem by fast geometric algorithms. The main idea is to define an atomic model for the protein structure and to exploit all known geometric angle and distance information along with the semi-quantitative short-range experimental information from NMR. We give an overview of the development of computational methods aimed at solving the problem either by metric matrix distance geometry or using other methods such as simulated annealing. We also discuss future demands and perspectives for structural calculations using NMR data. The need of determining larger and more complex protein structures implies the strong necessity of developing new methods for structural calculation with sparse data.