FLUCTUATION AND CROSS-CORRELATION ANALYSIS OF PROTEIN MOTIONS OBSERVED IN NANOSECOND MOLECULAR-DYNAMICS SIMULATIONS

Nanosecond molecular dynamics simulations of bovine pancreatic trypsin inhibitor and lysozyme in water are analyzed in terms of backbone ato mic positional fluctuations and dynamical cross-correlations. It is fo und that although the molecular systems are stable, B-factors calculat ed over a time period as long as 500 ps are not representative for the motions within the proteins. This is especially true for the most mob ile residues. On a nanosecond time-scale, the B-factors calculated fro m the simulations of the proteins in solution are considerably larger than. those obtained by structure refinement of the proteins in crysta ls, based on X-ray data. The time evolution of the atomic fluctuations shows that for large portions of the proteins under study atomic posi tional fluctuations are not yet converged after a nanosecond. Cross-co rrelations do not converge faster than the fluctuations themselves. Mo st display very erratic behavior if the sampling covers less than abou t 200 ps. It is also shown that inclusion of mobile atoms into the pro cedure used to remove rigid-body motion from the simulation can lead t o spurious correlations between the motions of the atoms at the surfac e of the protein. (C) 1995 Academic Press Limited