Dept. Of Life Science, Bar Ilan University, Ramat-Gan, 52900, ISRAEL
The three dimensional structure of proteins is complex and exquisite. Thus, it is widely assumed that the native conformation of proteins is in the global minimum of free energy. This assumption is in conflict with the notion, which is based among other evidences on theoretical computer-science considerations, that for a folding chain finding such a global minimum for arbitrary sequences is very difficult. A plausible explanation to this conflict is to suggest that evolution have played a major role in selecting those sequences that have the ability to fold. We investigate, in a very simple lattice model of proteins, possible evolutionary mechanisms that select for sequences with better stability and foldability. We start with a conformation which is in a local minimum of free energy, we follow the evolution of its corresponding sequences, and analyze the conditions under which the local energy minimum evolve into the global minimum of free energy. We found that by applying evolutionary pressure on a protein to become optimal within a limited set of its structural neighbors, the global ranking of this protein is greatly improved. We discuss possible implications of the work, and address the question of how to test these implications in real proteins.