BOLTZMANN PRINCIPLE, KNOWLEDGE-BASED MEAN FIELDS AND PROTEIN-FOLDING - AN APPROACH TO THE COMPUTATIONAL DETERMINATION OF PROTEIN STRUCTURES

The data base of known protein structures contains a tremendous amount of information on protein-solvent systems. Boltzmann's principle enab les the extraction of this information in the form of potentials of me an 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 whic h are useful in the development of knowledge-based force fields. Among the applications presented are the validation of experimentally deter mined protein structures, data base searches which aim at the identifi cation of native-like sequence structure pairs, sequence structure ali gnments and the calculation of protein conformations from amino acid s equences.