Molecular Dynamics of Nucleic Acids, Proteins, and Their Complexes: From Atomistic and Coarse-Grained Descriptions to New Methodologies
Computational modeling of biological macromolecules through molecular dynamics (MD) simulations is becoming increasingly useful to interpret the experimental results and guide the future experiments. Over the last decade, MD simulations have become much more powerful and accessible due to advancements in fields of structural biology, computer science and integrated chip design. In this thesis, I utilize different MD simulation techniques to model interaction of and antiviral mechanisms. Within the framework of nucleic acid modelling, we describe first dynamics of small circular single stranded nucleic acids and highlight key dynamical differences of backbone behavior in solution between DNA and RNA and their ability to capture ions for much longer timescales as compared with linear nucleic acids. Second, we model single stranded DNA corona on carbon nanotubes (CNT) and quantify the number of nucleotides that cover CNTs. Third, we modelled melting mechanisms of DNA duplexes on laser-excited gold nanoparticles, which can provide control over heating in biological systems through laser-based sources. Within the framework of modeling of antiviral mechanisms, first, I describe computational models of APOBEC3G protein, which is known to restrict HIV-1 virus, and examine its interactions with ssDNA. Next, we model broad-spectrum antivirals nanoparticles, mimicking heparan sulfate proteoglycans against human papillomavirus (HPV) in which we identify viral capsid regions that facilitate binding with such nanoparticles. Lastly, I propose peptide-based therapeutics for fast mutating SARS-CoV-2 virus and design an adaptive algorithm to generate peptide templates against different mutants of SARS-CoV-2.
Chemistry|Computational chemistry|Biochemistry|Molecular biology
Chaturvedi, Parth, "Molecular Dynamics of Nucleic Acids, Proteins, and Their Complexes: From Atomistic and Coarse-Grained Descriptions to New Methodologies" (2021). ETD Collection for University of Texas, El Paso. AAI28650124.