CAREER: Development and Application of Multi-scale Modeling for Biomolecular Association

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The objective of this project is to investigate complex interactions among molecules, including proteins, enzymes and nanoparticles using computer modeling. Understanding association processes will increase fundamental understanding of protein-ligand binding and its applications. Along with binding, molecule's kinetic behavior - how they move - also plays a crucial role in understanding how rapidly they interact, undergo change, and bind with one another. Traditional approaches in protein binding and enzymology typically focus on a final chemical-protein structure, instead of the kinetic and binding processes that precede that final stage. Yet, exploring binding processes deepens our understanding of how molecules recognize binding partners, and will guide molecular designs and engineering of enzymes for more efficient chemical catalysis. Simulations have provided powerful tools to study molecular associations. However, real molecular systems are quite complicated, and these tools are usually either very time consuming or tend to over-simplify a biological system. This project will combine multi-level coarse-grained and atomistic simulations to efficiently and accurately model molecular associations and kinetic enhancement of the enzymes and nanoparticle systems. Reliable and efficient molecular simulations play an ever-increasing role in studying binding kinetics. They provide unique insights into the mechanisms of biomolecular activity, an in the integration and interpretation of experiments. In addition, understanding binding kinetics contributes to the design of novel molecules and engineering enzymes and enzyme complexes for more efficient chemical activity. Successful completion of this research will improve understanding of protein-ligand binding kinetics and assist the design of nanostructures, nanoparticles and engineered enzymes.This project will train young scientists, including graduate, undergraduate, and high school students. Seminars and summer courses will be organized to train students from the local colleges, high schools and UC Riverside. The outreach program will broaden participation of underrepresented groups by supporting under-represented minority students in science. Summer courses and seminars will introduce the field of computational chemistry and provide hands-on help for students doing research in the PI's laboratory. The results of this project will be integrated into regular courses at UCR and in special courses/seminars. The methods developed in the project will deepen understanding of protein-ligand recognition and binding kinetics. These are important in molecular design; therefore, the work will have practical benefits in various areas such as chemistry, biology, engineering and environmental sciences.