Development of Computational Tools and Their Applications to Various Biological Systems

PROJECT SUMMARY Biological macromolecules work together in a complex network to carry out essential cellular functions in living organisms. Understanding this complex network of interactions at the molecular level by developing necessary computational tools is an all-encompassing goal of our laboratory. This proposal aims to continue such efforts

particularly on CHARMM-GUI for the biomolecular modeling and simulation community, G-LoSA-related tools for structural systems pharmacology, and GlycanStructure.ORG for glycan modeling and simulation and glycan binding site prediction. First, CHARMM-GUI has become an essential web-based cyberinfrastructure for

constructing complex biomolecular simulation systems. We will further develop and expand its functionality to support more force fields, QM/MM interface for enzymatic catalysis reactions, more advanced simulation methods, API development, and DOI assignment. Second, we will continue to expand the application of our

local-structure centric computational toolset, G-LoSA (Graph-based Local Structure Alignment), for the studies of protein-ligand interactions at the proteomic level. Our local structure refinement method will be extended to include protein-protein binding interfaces to further elucidate conserved local surface regions of protein-protein

interactions that are crucial in biological processes. Third, our glycan modeling and simulation toolset will be extended to glycan binding pose prediction, glycan binding site prediction, and glycan binding site optimization for rational design and refinement of a known or potential glycan binding site. The successful completion of this

project is expected to provide a large and unique scope of research software tools for the biomedical research community to carry out innovative and novel biomolecular modeling and simulation research for the prevention and treatment of human disease.