Jay Ponder of Washington University in Saint Louis and David Gohara of Saint Louis University are supported by an award from the Chemical Theory, Models and Computational Methods program in the Division of Chemistry, and the Office of Cyberinfrastructure to improve the accuracy of the AMOEBA (Atomic Multipole Optimized Energetics for Biomolecular Applications) force field model for molecular simulation and to increase the range of applicability of the model via parallelization of the underlying TINKER molecular modeling software. In this project, the researchers develop new terms for an AMOEBA-2 model that encompass physical effects missing from the original AMOEBA force field. In particular, charge transfer, penetration effects and damped short-range dispersion terms are being parameterized to remove the largest remaining systematic inaccuracies. Comparison of the resulting short-range energetic model against quantum mechanical calculations allow correct partitioning of internal energy into the various terms, and provide a consistent basis for improving AMOEBA-2. The existing TINKER code as well as the new energy terms are being parallelized using a hybrid OpenMP and MPI paradigm. The resulting new potential and software will be applied to two current problems that require both extensive simulation and a high level of accuracy: prediction of organic crystal structures, and computation of ligand binding in host-guest complexes. Both of these problem areas have long represented "holy grail" applications for the field of computational chemistry.
Molecular force field calculations are important tools in computational biophysics, structure determination of bio-macromolecules, molecular design, and modeling of the properties of molecules and materials. Methods, algorithms and software developed under this project are being made available to the broader community via periodic release of new versions of the TINKER molecular modeling package. This package is widely used in academic research labs and in the chemical and pharmaceutical industries worldwide. The team is also involved in educational activities through University courses, as well as the provision of tutorial materials and laboratory exercises for instructors wishing to use the TINKER software in their own teaching.
