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Molecular dynamics simulations of peptide and protein systems




Weber, Ryan Nicholas, author
McCullagh, Martin, advisor
Szamel, Grzegorz, committee member
Finke, Richard, committee member
Wang, Qiang, committee member

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Molecular systems composed of amino acids play an important role in biological systems and have numerous functions and applications due to their enormous chemical versatility. These systems are usually divided into peptides and proteins based on the number of amino acids that compose each molecule. Molecular dynamics simulations can provide molecular-level insights into the self-assembly of peptide systems and the function of protein systems where experimental methods fail. Peptides are utilized for their switchable and self-assembling properties for the engineering of novel biomaterials which are responsive to external stimuli. Often, peptides are paired with aromatic molecules to incorporate interesting optoelectronic properties into the material. Chapter 2 discusses a molecular dynamics simulation study on the self-assembling properties of the self-complimentary (RXDX)4 sequence paired with an unnatural coumarin amino acid for the design of a pH-switchable, optoelectronic, self-assembling biomaterial. Specifically, it is found that the hydrophobicity of the peptide sequence plays a significant role in the stability and pH-switchability of (RXDX)4 and coumarin-(RXDX)4 β-sheet fibers. Proteins are essential to all known life and participate in nearly every cellular process. There are many varieties of proteins with important diverse functions. Helicase proteins hydrolyze NTP to catalyze the translocation and unwinding of double-stranded nucleic acids such as RNA and DNA and play a critical and extensive role in viral replication. Nsp13 is a helicase protein that is an important component of the viral replication machinery of the severe acute respiratory syndrome coronavirus-2 and remains a promising target for antiviral drugs. Chapter 3 presents a molecular dynamics simulation study on the ATP-dependent translocation mechanism of the SARS-CoV-2 nsp13 helicase. Specifically, the results from the study suggest that nsp13 may translocate using an inchworm stepping mechanism and that the binding of ATP may cause the first step in the translocation cycle. Motifs Ia, IV, and V are identified as key motifs in the translocation mechanism of nsp13 and as potential targets for the development of antiviral drugs against SARS-CoV-2. Although molecular dynamics simulation is a powerful approach to investigate condensed phase molecular phenomenon such as protein folding, allostery, and self-assembly, molecular dynamics is limited in the size and length of simulations that can be performed. Implicit solvent simulation methods, such as Implicit Solvation using the Superposition Approximation (IS-SPA), were developed to address these issues in solvated systems. The goal of IS-SPA is to improve the efficiency of molecular dynamics simulations by removing the solvent from the system, but still include the effect of the solvent on the solute. Chapter 4 presents the development and optimization of an IS-SPA molecular dynamics code on a GPU using CUDA. Specifically, the performance of three different IS-SPA CUDA algorithms are compared. The future studies of the self-assembly of peptide systems for the design of biomaterials, the ATP-dependent translocation mechanism of the SARS-CoV-2 nsp13, and the optimization of the GPU-capable IS-SPA molecular dynamics code in CUDA are discussed in the final chapter.


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molecular dynamics


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