Molecular Dynamic Simulation of Bio-molecular Dynamics, Folding, and Assembly

Download or read book Molecular Dynamic Simulation of Bio-molecular Dynamics, Folding, and Assembly written by Rongzhong Li and published by . This book was released on 2015 with total page 101 pages. Available in PDF, EPUB and Kindle. Book excerpt: It remains a major challenge in molecular biophysics to understand how biomolecules fold and interact with each other to carry out their cellular processes in a functional organism. Computational molecular dynamics (MD) simulations are indispensible tools for characterizing biomolecular processes at the microscopic level. In this thesis, I will present three distinct MD simulation studies of RNA folding, protein-RNA assembly, and protein-nanoparticle interaction mechanisms with direct comparisons to experiments whenever possible. I first present a coarse-grained and empirical force field MD simulations of tRNA. The coarse-grained MD simulations are based on the funneled energy landscape theory of biomolecular folding, and we perform tRNA folding TIS model MD simulations of four E. coli tRNAs with distinct sequences but very similar secondary and tertiary structures. The folding mechanisms are highly dependent on a sequence dependent base-stacking interaction term, demonstrating that the stabilities of the individual loops and stem determine the folding mechanism. We also matched melting profiles with classical empirically observed ones. The secondary structural elements can form in parallel if their stabilities are sufficiently similar, and this may explain why tRNAs have been shown experimentally to have fast and slow folding rates. We also observe the premature folding of some loops that must backtrack and completely unfold before folding to the native state can proceed. The backtracking mechanism has been predicted by simulations and verified in experiments in proteins, and our study is the first to predict the scenario for RNA molecules and it amenable to verification by experiments. Next, I present preliminary development of a novel protein-RNA complex assembly model for coarse-grained MD simulations. The model is applied to aminoacyltRNA synthetase in complex with its cognate tRNA molecule, specifically, a modeled MetRS:tRNA[superscript fMet] complex. The model is based on the native structure based Go-type model for proteins and the TIS model for RNA, but the introduction of the protein-RNA interactions is not trivial. Also, since these models were developed independently, matching their stabilities is a challenge. In our Go-TIS model Hamiltonian, we introduce protein-RNA interactions based on the Lorentz-Berthelot mixing rules and matched the empirical stabilities of the MetRS and tRNA[superscript fMet] separately. The model is not yet complete and we still have issues with regard to the binding stabilities. Finally, I present our novel GPU-optimizedMD simulation model of protein-nanoparticle interactions that was developed in collaboration with an experimental group. In this model, we use the Go-type model for proteins with an electrostatic term to describe the interactions between the charged residues and the charged citrate coated spherical nanoparticle. In excellent agreement with CD spectra, we observe the binding of the proteins to the nanoparticle surface, resulting in the melting of the secondary structure, notably the [alpha symbol]-helices. The percentage of helical melting is in quantitative agreement with our coarse-grained MD simulations.