New theoretical techniques are often coupled with software and hardware development, such as the generation of new simulation techniques and the systematic testing and evaluation of methods. Specific projects include: - Development of Langevin Piston methods for NPT simulation of periodic systems and for stochastic boundary molecular dynamics (MD) simulations - Development of quantum mechanical potentials and appropriate algorithms for use in molecular dynamics simulations - Determination of protein structure by NMR and molecular modelling - Development of an optimized protocol for the preparation of low temperature states - Development of flexible MD techniques that remove high-frequency degrees of freedom - Development of the REPLICA/PATH method for determining reaction paths in complex systems using simulated annealing - Free energy perturbation simulations in solution, examining the effect of restraints -Conversion of physical models into three-dimensional coordinates for computer analysis and simulation - Development of ray-traced molecular graphics software for HP workstations, high-resolution color printers and for movies using NTSC video equipment - Adaptation of a Truncated Newton minimizer for CHARMM and biomolecular applications. Parameter sets and models are generally available for most macromolecular systems, but there is considerable room for improvement, and alternate models that improve realism, or reduce computational costs, need to be examined. This effort involves the refinement of parameters and the exploration of alternate energetic models for molecules and environmental conditions. Ongoing projects include: - Evaluation of parameter sets - Approximation of long-range interactions in macromolecular simulation variants of the Ewald Sum method, using a particle mesh grid - New methods for long-range truncation of the energy potential - Evaluation and comparison of implicit and explicit water models for simulations examining the hydration of proteins - Molecular dynamics simulation studies of DNA:analysis of the parameter sets using an infinite DNA helix
