Density Functional Theory for van der Waals Interactions

DESCRIPTION (provided by applicant): Q-Chem is a state-of-the-art commercial quantum chemistry program that is used to model atomic and molecular processes over a wide range of disciplines, including biology, chemistry, and materials science. Among the quantum chemistry methods, density functional theory (DFT) is perhaps the most widely used, especially in molecular biology, due to its ability to accurately model a wide range of molecular systems with reasonable computational cost. Despite its wide use, DFT does not include the dispersion correlation effect, or van der Waals interaction, which plays a critical role in the determination of the overall conformations of molecular systems and accordingly, is indispensable in the study of DNA and proteins, molecular recognition, the packing of crystals, etc. In Phase I of this project, we developed an efficient SCF and nuclear gradient solution for a density functional dispersion model called XDM, and demonstrated that it corrected some of the failures of current DFT methods in structural and energetic studies. In this Phase II proposal, we plan to incorporate dispersion of the XDM model into all the major aspects of DFT applications, including energetic and structural calculations of both ground and excited electronic states, with further improved accuracy. To demonstrate the utility of the DFT-XDM approach for modeling systems of biological interest, we will investigate two challenging molecular processes, namely the binding process of cisplatin to DNA, and electronic transitions in photoactive yellow protein (PYP). Cisplatin is widely used in chemotherapy, and photoactive yellow protein is a widely studied photoreceptor that is key to understanding signal transduction. As we will show, the successful development and implementation of the DFT-XDM model proposed here will lead to much more accurate DFT solutions. PUBLIC HEALTH RELEVANCE: This project aims to develop and implement a very accurate DFT method. DFT is at the core of molecular modeling and is applied widely in biological research/development and in drug discovery. The improved DFT will significantly increase researchers' quality of work and extend the application scope of DFT.