Structure and Property of Polymers and Biopolymers from Molecular Dynamic Simulations

Natural and synthetic polymers and biopolymers have been studied for a variety of applications in food emulsion, biopharmaceutical purification, tissue engineering, and biosensor. The structure and property of polymers and biopolymers are critically important to determine their functions. Molecular dynamics (MD) simulations have a unique advantage to explore the structure and property of polymers and biopolymers from the molecular level. In the dissertation, MD simulations were conducted to study the mechanisms of various biological and chemical processes controlled by polymers and biopolymers based on real-world experimental results. Seven heptapeptides have been screened from a peptide library in our earlier study of the antibody purification. They have substantial binding affinities to the Fc fragment of IgG. In Chapter 2, the binding mechanisms between seven heptapeptides and the Fc fragment have been investigated by protein-ligand docking, free energy calculation and MD simulations. It is the first time that glycan residues are found to be the binding pocket for small ligands. The novel binding pocket is different from the CBS binding site for protein A and protein G. We also found out that, the results of free energy calculations are in good agreement with the ELISA experiments. The thermos-responsive polymer, PVCL (poly(N-vinylcaprolactam)) was grafted on the surface of a membrane as the responsive hydrophobic chromatography for the protein purification in our earlier study. In Chapter 3, significant efforts have been devoted to develop the force field parameters for PVCL. The coil-to-globule conformational transition of PVCL has been successfully observed in MD simulation for the first time. The water dynamics analysis provides significant insights into the interaction between PVCL and water molecules. The novel statistical analysis of VCL ring conformations and the distribution along backbone also elucidate the steric requirement in the coil-to-globule transition. In Chapter 4, MD simulations were conducted to investigate the biocompatibility, energetics and interaction mechanisms between the PVCL polymer chains and bovine serum albumin (BSA) in 1M NaCl and aqueous solutions. Water structures surrounding the polymer chains and BSA as well as their hydrogen bonding, electrostatic and van der Waals interactions were determined. Significant insights were obtained on the effects of polymer hydration state, polymer chain length as well as the presence of salt ions on the protein-ligand interactions. A novel polymeric solid acid catalyst consisting of two polymer chains grafted on a substrate for biomass hydrolysis was successfully synthesized. A poly (styrene sulfonic acid) (PSSA) polymer chain is immobilized on a substrate and used to catalyze biomass hydrolysis. A neighboring poly (vinyl imidazolium chloride) ionic liquid (PIL) polymer chain is grafted to help solubilize lignocellulosic biomass and enhance the catalytic activity. To elucidate mechanistically the catalytic actions and further optimize its performance, interactions among the PSSA, PIL, and cellulose chains were investigated using MD simulations in Chapter 5. Moreover, the free energies surfaces for the interactions between polymer chains and cellulose substrate were determined using combined MD and Metadynamics (MTD) simulations. The research clearly demonstrate that the solvent plays a critical role in the cellulose hydrolysis reaction catalyzed by novel enzyme mimic polymeric catalysts PSSA and PIL. It is found that PSSA chain is likely to form partially dehydrated interaction with cellulose in both aqueous and [EMIM]Cl solutions. PIL plays an important role to prevent the completely dehydrated interactions and facilitate partially dehydrated interaction between PSSA and cellulose chains. Acknowledgement I would like to express my sincere gratitude to my advisor Prof. Xianghong Qian for her motivation, patience and support for my Ph.D. study. Her guidance helps me in my research, presentation and writing. I could not thank enough for her insightful comments and encouragement for making me grow to an independent researcher. Thank you for bringing me into the molecular modeling research field. Besides my advisor, I would like to thank my dissertation committee: Prof. Raj Raghavendra Rao, Prof. Kartik Balachandran and Prof. Ranil Wickramasinghe. Thanks for your time to attend my defense, and your comments that broaden my research from many perspectives. My thank also goes to my coworkers Dr. Hongbo Du, who taught me the fundamentals of simulations, Dr. Anh Vu, Dr. Justin Weaver, and Dr. Zizhao Liu who supplied me the excellent experimental results. I want to thank all other group members who helped me in my research. Financial support from National Science Foundation is gratefully acknowledged. The travel grant from graduate school of University of Arkansas really provides my precious opportunities to present my work and network with people working in different fields. Last but not the least, I would like to thank my wife and baby boy for supporting my Ph.D. study. Your love always keeps me moving forward to my future. Table of