HIGHLY CONSTRAINED MULTIPLE-COPY REFINEMENT OF PROTEIN CRYSTAL-STRUCTURES

In the course of refining atomic protein structures, one often encount ers difficulty with molecules that are unusually flexible or otherwise disordered. We approach the problem by combining two relatively recen t developments: simultaneous refinement of multiple protein conformati ons and highly constrained refinement. A constrained Langevin dynamics refinement is tested on two proteins: neurotrophin-3 and glutamine sy nthetase, The method produces closer agreement between the calculated and observed scattering amplitudes than standard, single-copy, Gaussia n atomic displacement parameter refinement. This is accomplished witho ut significantly increasing the number of fitting parameters in the mo del, These results suggest that loop motion in proteins within a cryst al lattice can be extensive and that it is poorly modeled by isotropic Gaussian distributions for each atom, (C) 1997 Wiley-Liss, Inc.