FOLDING OF THE HUMAN PROTEIN FKBP - LATTICE MONTE-CARLO SIMULATIONS

Monte-Carlo simulations of folding of the human protein FKBP are prese nted. The protein is confined in a simple cubic lattice and only neare st-neighbour interactions are considered. The evolution of protein str ucture, energy and diameter is followed over time. Starting from diffe rent extended conformations, compact globular forms with a hydrophobic core are reached above a critical temperature T-c, while below T-c th e protein 'freezes' into high-energy, non-compact states. In the tempe rature range of folding, all the recorded intermediate states belong t o two structural groups, where the process spends most of its time, se parated by relatively fast transitions. During folding, the protein is successively composed of three and two compact fragments, whose separ ation occurs at loop positions. From comparisons performed on a domain of the family sharing 24 % identity with FKBP, it appears that the nu mber of fragments, and therefore their location, are sequence dependen t. (C) Academie des sciences / Elsevier.