A FAST AND EFFICIENT PROGRAM FOR LOOPS. Yuzhen Han, Hongyu Zhang, Luhua Lai, Leyu Wang and Youqi Tang, Institute of Physical Chemistry, Peking University, Beijing 100871, China

We developed an efficient Monte Carlo Simulated Annealing (MCSA) program for modelling protein loops with high speed. The total conformational energy in each step of MCSA simulation consists of two parts: the nonbonded atomic interaction represented by a simple softsphere potential and the harmonic distance constraint to ensure the smooth connection of the loop segment to the rest protein structure. The softsphere potential was a quite simplified potential that has been successfully used by the authors in modelling the carbohydrate part of glycoprotein systems. It only considers the purely repulsive steric interactions to avoid artificial attractive forces between the atoms in the absence of solvent molecules in modelling. The N-terminal of the loop segment was connected to the bulk protein part, and two dummy main chain atoms N and C[[alpha]] immediately following the C-terminal of the loop segment were constrained to their real positions in the crystal structure, which not only assures the correct geometry of loop-protein connection but also is more rigorous than the previous work. To improve the speed, two strategies, local region method and grid-mapping method, were devised to accelerate the computing of environmental interaction that is responsible for the major part of the computing consumption. The grid-mapping method can reduce computing time dramatically. Conformations with rational steric packing and smooth connection to the rest protein structure were generated by the MCSA program, and then were refined in the empirical force field CHARMm. Finally, we got the conformations with high precision to the crystal structure for all the loops of bovine pancreatic trypsin inhibitor (BPTI). With the criteria of CHARMm energy, near-native conformations can be selected, for example, the backbone root mean square deviation (RMSD) 0.93 Å from the crystal structure was gotten for the longest 9-residue loop.