Folding of the human protein FKBP. Lattice Monte-Carlo simulations

Monte-Carlo simulations of folding of the human protein FKBP are presented. The protein is confined in a simple cubic lattice and only nearest-neighbour interactions are considered. The evolution of protein structure, energy and diameter is followed over time. Starting from different extended conformations, compact globular forms with a hydrophobic core are reached above a critical temperature Tc, while below Tc the protein 'freezes' into high-energy, non-compact states. In the temperature range of folding, all the recorded intermediate states belong to two structural groups, where the process spends most of its time, separated by relatively fast transitions. During folding, the protein is successively composed of three and two compact fragments, whose separation occurs at loop positions. From comparisons performed on a domain of the family sharing 24% identity with FKBP, it appears that the number of fragments, and therefore their location, are sequence dependent.