Boltzmann's principle, knowledge-based mean fields and protein folding. An approach to the computational determination of protein structures

Abstract

The data base of known protein structures contains a tremendous amount of information on protein-solvent systems. Boltzmann's principle enables the extraction of this information in the form of potentials of mean force. The resulting force field constitutes an energetic model for protein-solvent systems. We outline the basic physical principles of this approach to protein folding and summarize several techniques which are useful in the development of knowledge-based force fields. Among the applications presented are the validation of experimentally determined protein structures, data base searches which aim at the identification of native-like sequence structure pairs, sequence structure alignments and the calculation of protein conformations from amino acid sequences.