Methods have been developed for the determination of vibrational frequencies and normal modes of large systems in the full conformational space (including all degrees of freedom) and in a reduced conformational space (reducing the number of degrees of freedom). The computational method, which includes Hessian generation and storage, full and iterative diagonalization techniques, and the refinement of the results, is presented. A method is given for the quasiharmonic analysis and the reduced basis quasiharmonic analysis. The underlying principle is that from the atomic fluctuations, an effective harmonic force field can be determined relative to the dynamic average structure. Normal mode analysis tools can be used to characterize quasiharmonic modes of vibration. These correspond to conventional normal modes except that anharmonic effects are included. Numerous techniques for the analyses of vibrational frequencies and normal modes are described. Criteria for the analysis of the similarity of low-frequency normal modes is presented. The approach to determining the natural frequencies and normal modes of vibration described here is general and applicable to any large system. 0 1995 by

Motivation: Exploitation of locally similar 3D patterns of physicochemical properties on the surface of a protein for detection of binding sites that may lack sequence and global structural conservation.Results: An algorithm, ProBiS is described that detects structurally similar sites on protein surfaces by local surface structure alignment. It compares the query protein to members of a database of protein 3D structures and detects with sub-residue precision, structurally similar sites as patterns of physicochemical properties on the protein surface. Using an efficient maximum clique algorithm, the program identifies proteins that share local structural similarities with the query protein and generates structure-based alignments of these proteins with the query. Structural similarity scores are calculated for the query protein's surface residues, and are expressed as different colors on the query protein surface. The algorithm has been used successfully for the detection of protein–protein, protein–small ligand and protein–DNA binding sites.Availability: The software is available, as a web tool, free of charge for academic users at http://probis.cmm.ki.siContact: dusa@cmm.ki.siSupplementary information: Supplementary data are available at Bioinformatics online.

Vibrational spectroscopy studies show that the bulk water bending band becomes narrower with increasing temperature (Maréchal, Y. J. Mol. Struct. 1994, 322, 105). Since this counterintuitive effect is not associated with the quantum nature of nuclear motion a molecular dynamics (MD) simulation is expected to reproduce it even in the classical limit. We have performed a classical MD simulation of the flexible simple point charge (SPC) and extended SPC (SPC/E) water models to determine the temperature dependence of the bulk water vibrational spectrum. The intramolecular water potential proposed by Toukan and Rahman, including a stretch−bend coupling term, was applied. We performed MD simulations at −4 and 80 °C to compare the calculated vibrational spectra, in particular, the band associated with the bending mode, with the experiment. The experimentally determined narrowing of the bending band with increasing temperature is not reproducible by MD simulation with the applied force field. However, the results show that this approach successfully reproduces all other experimentally observed spectroscopic properties of bulk water.

The new symplectic molecular dynamics (MD) integrators presented in the first paper of this series were applied to perform MD simulations of water. The physical properties of a system of flexible TIP3P water molecules computed by the new integrators, such as diffusion coefficients, orientation correlation times, and infrared (IR) spectra, are in good agreement with results obtained by the standard method. The comparison between the new integrators' and the standard method's integration time step sizes indicates that the resulting algorithm allows a 3.0 fs long integration time step as opposed to the standard leap-frog Verlet method, a sixfold simulation speed-up. The accuracy of the method was confirmed, in particular, by computing the IR spectrum of water in which no blueshifting of the stretching normal mode frequencies is observed as occurs with the standard method.