FINDING THE LOW-ENERGY FORMS OF AVIAN PANCREATIC-POLYPEPTIDE WITH THEDIFFUSION-PROCESS-CONTROLLED MONTE-CARLO METHOD

Ab initio folding of the avian pancreatic polypeptide using a diffusio n-process-controlled Monte Carlo method is presented. This method diff ers from other Monte Carlo methods in that two successive conformation s must be kinetically connected in a small period of time. The 36-resi due polypeptide is represented using a hybrid level of structure descr iption: the backbone is treated at an all-atom level, while the side c hains are modeled as spheres. The conformations are evaluated on the b asis of pairwise contact energies between the side chains, a main chai n hydrogen bonding potential, and local bonded potentials. Starting fr om various extended conformations, the chain reaches the basin of lowe st energy in similar to 1000-3500 Monte Carlo steps and the predicted conformations deviate by similar to 3.0 Angstrom rms from the x-ray st ructure. The eight trajectories suggest a three-step mechanism: (1) ea rly formation of the alpha helix in the region 14-33, (2) cooperative formation of long-range interactions, and (3) stabilization of the pol yprolinelike conformation in the-region 1-8 in the final steps of fold ing. (C) 1998 American Institute of Physics.