HARMONIC-ANALYSIS OF LARGE SYSTEMS .3. COMPARISON WITH MOLECULAR-DYNAMICS

Atomic motions in bovine pancreatic trypsin inhibitor (BPTI), derived from molecular dynamics, harmonic analysis, and quasiharmonic analysis , are compared when a single protein model, energy parameters, and env ironment are employed. Molecular dynamics (MD) was carried out for 2 n anoseconds. An average structure was determined from the last nanoseco nd of the MD simulation, when no major structural changes were observe d. This structure was used for several harmonic analysis calculations as well as for a reference structure for the quasiharmonic analysis, f or both full basis and reduced basis sets. In contrast to the harmonic analysis results, the quasiharmonic reduced basis calculation using a spherical harmonics reduced basis provided good agreement with the fu ll basis calculation, suggesting that when anharmonic effects are cons idered, BPTI can behave as a homogeneous object. An extensive analysis of the normal modes from a diverse set of 201 minimized MD simulation frames was performed. On only the sub-picosecond time scale were ener gy minima revisited after a transition to another state. This analysis shows that the dynamics average structure is not representative of th e simulation frames in terms of energy and vibrational frequencies. Fo r this model of BPTI, 42% of the motion (mean-squared fluctuation) can be attributed to harmonic limit behavior. A spectral analysis of the correlation function of deformation for a particular normal mode or qu asiharmonic mode can be used to determine the time scales of motions w hich correspond to harmonic vibration, large-scale drift, or sharp tra nsitions between local substrates. (C) 1995 by John Wiley & Sons, Inc.