Research Project
2378284
Ab initio quantum chemistry methods are now both accurate and practical when applied to gas phase calculations, but useful applications of these techniques to most biological and biomedical processes will not be feasible until they can be used for realistic and precise calculations of solvated systems. Schrodinger, Inc. proposes to use its PS-GVB code, a reliable and efficient general purpose ab initio electronic structure program, together with the self-consistent reaction field (SCRF) methodology developed in Phase I of this research, to treat complex biological systems in solution. The Phase II research described in this proposal will address the key barriers to routine use of computational methods for drug binding and other biomedical and biochemical applications. The accuracy of continuum models for solvated systems will be substantially improved with hydrogen bonding corrections. Schrodinger then plans to combine the SCRF code with the macromolecular simulation package MacroModel, simultaneously implementing recent advances in the use of multiple timescales in molecular dynamics. PROPOSED COMMERCIAL APPLICATION: The extensions of quantum mechanical computational methods described here will permit practical and inexpensive evaluations of the properties of candidate drug molecules. Consequently, we expect substantial commercial interest in this software, particularly from the pharmaceutical industry.
