DEVELOPMENT AND APPLICATION OF EFFECTIVE FRAGMENT POTENTIALS FOR (BIO)MOLECULAR SYSTEMS

The Effective Fragment Potential (EFP) is a quantum-mechanical based model potential for accurate calculations of non-covalent interactions between molecules. It can be coupled with ab initio methods in so-called QM/EFP models to explore the electronic properties of extended molecular systems by providing rigorous description of surrounding environments. The current EFP formulation is, however, not well suited for large-scale simulations due to its inherent limitation of representing effective fragments as rigid structures. The process of utilizing EFP method for the molecular systems with flexible degrees of freedom entails multiple sets of parameter calculations requiring intensive computational resources. This work presents development of the EFP method for describing flexible molecular systems, so-called Flexible EFP. To validate the applicability of the Flexible EFP method, extensive benchmark studies on the amino acid interactions, binding energies, and electronic properties of flavin chromophore of the cryptochrome protein have been demonstrated. In addition to methodological developments, excitonic properties of the Fenna-Matthews-Olson (FMO) photosynthetic pigment-protein complex are explored. In biological systems where intermolecular interactions span a broad range from non-polar to polar and ionic forces, EFP is superior to the classical force fields. In the present study, we demonstrate excellent performance of the QM/EFP model for predicting excitonic interactions and spectral characteristics of the FMO wildtype complex. We characterize the key factors for accurate modeling of electronic properties of bacteriochlrophyll a (BChl a) photosynthetic pigments and suggest a robust computational protocol that can be applied for modeling other photosynthetic systems. Developed computational procedures were also successfully utilized to elucidate photostability and triplet dynamics in the FMO complex and spectroscopic effects of single-point mutagenesis in FMO. A combination of polarizable EFP molecular dynamics and QM/EFP vibrational frequency calculations were also applied to understanding and interpreting structures and Raman spectroscopy of tert-butyl alcohol solutions.