Software for DFT Calculations in Solution and Proteins

Our goal is to provide a superior computational tool for quantitative analysis of the structure-fun-ction relationships in proteins and of chemical and biochemical reactions in aqueous solutions. Theapplicants plan to achieve this goal by combining the most advanced approach of computationalquantum mechanics (Density Functional Theory, DFT) and recently developed methods of treatment ofsolvation effects based on classical electrostatics and continuum theory. In Phase I the following stepswill be undertaken to develop, validate and test the software: 1) a prototype software for evaluation ofhydration effects on small quantum mechanical systems in solution will be developed and applied tocalculation of hydration energies and solution dipole moments of small molecules for which experimentaldata is available; dependence of the results on the basis sets and parameters of the continuum theorywill be studied; (2) as accurate a representation as possible of the electron density is critical for thesuccess of the computations, advanced methods of Distributed Multiple Analysis (DMA) will be testedwith DFT to evaluate effects of accurate multiple expansion of the results; (3) classical multipoles andatomic polarizabilities of a protein-like medium will be self consistently introduced into DFT along withthe solvent reaction field to allow both continuum and atomic representations of the environments ofprotein active sites. (4) We will test calculations to be performed for the enzymatic mechanism of serineproteases to compare DFT results with published results of experimental and theoretical studies. Thesystem will be simplified to make computations feasible within the time frame of the Phase I of theproposal. (5) The prototype software will be given for independent testing and evaluation of its scientificand commercial merits to a few established research groups and a commercial software company. Onesuch company, Biosym, is interested in rights for the software developed under this project.