Understanding the Role of Surface and Solvent on Biomolecular Structure and Dynamic

Biomolecules have been used in many applications including biosensors and biocatalysts due to their unique recognition and catalytic properties. An understanding of biomolecular structures and dynamics is important because the structural stability of biomolecules is heavily related to their functionality and performance in these applications. This work focused on developing a fundamental understanding of how biomolecules respond under various conditions. More specifically, the goals of this study were (1) to understand the effect of solvent, surface, and structure on the behavior and properties of a single-stranded DNA (ssDNA) and a lipase enzyme, Candida antartica Lipase B (CALB), and (2) to provide overall guidance for improvements of applications utilizing these biomolecules.;The structure and dynamics of ssDNA is crucial for cellular processes and also for the properties of DNA-based materials. In this thesis, we elucidated the dynamics of ssDNA as a function of its length and its behavior on surfaces as well as the mechanical stability of graphene on self-assembled monolayers (SAMs). All-atom molecular dynamics (MD) simulations revealed that ssDNA does not behave like an ideal chain due to internal nonbonded interactions, such as base pairing and stacking. We then examined the effect of graphene-based surface properties on the structure and dynamics of folded ssDNA. Simulation results suggested that surface oxidation can affect the structural stability of ssDNA. For example, folded ssDNA structures can be easily disrupted on graphene surfaces with low or high oxidation states; in contrast, ordered ssDNA structures can be maintained on surfaces with moderate oxidation states. We also showed that similar conclusions are applicable to other biomolecules, such as silk fibroin. Next, we focused on graphene surfaces on SAMs by conducting a combined computational and experimental study to delineate how the polarity of SAMs' head group can influence interfacial mechanical properties of graphene -- SAM heterostructures. MD simulations showed a good agreement with experiments and also indicate important phenomena occurring at the interfaces due to the role of interfacial water on the mechanical strength of heterostructures. Our study showed that hydrophobic SAMs are preferable over hydrophilic SAMs to achieve higher mechanical strength. Overall, the results of our simulations can provide a fundamental understanding of ssDNA and surfaces and aid in the selection of surfaces (e.g., optimal surface oxidation states for different applications).;CALB can catalyze complex chemical reactions for many high-value products. However, the choice of solvents as reaction media or amino acids for mutations is critical for biocatalysis processes; these choices can either enhance or diminish the stability of an enzyme's structure, which is crucial to its enzymatic activity. In this thesis, we propose the design rules for the selection of solvents and mutation sites that can increase CALB enzymatic activity. Specifically, simulation results elucidated the roles of cations/anions in ionic liquids on the structure of CALB; if an anion is strongly coordinated or if the size of a cation is too large or small compared to that of an anion, secondary structures around the catalytic cavity become disrupted and lead to poor enzymatic activity. Further simulations enabled us to pinpoint important mutation sites of CALB that cause exposure of the catalytic cavity, with an increase in activity. Based on these observations, a CALB variant with a 6-fold higher activity than the native enzyme was obtained. Overall, strategies designed by computational observations allowed us to narrow down the possible number of solvent choices and mutation sites, which allows for rational enzyme engineering.