Computational Methods in Biomolecules:Study of Hydrophilic Interactions in Protein Folding & Constant-pH Molecular Simulation of pH Sensitive Lipid MORC16

• Main Author: Zhang, Wei
• Format: Others
• Published: Scholarly Commons 2018
• Subjects: hydrophilic interaction; lipid; molecular simulation; MORC16; pH; protein folding; physical chemistry; pharmaceutical sciences; computational chemistry; Pharmacy and Pharmaceutical Sciences
• Online Access: https://scholarlycommons.pacific.edu/uop_etds/3145; https://scholarlycommons.pacific.edu/cgi/viewcontent.cgi?article=4144&context=uop_etds

Water molecules play a significant role in biological process and are directly involved with bio-molecules and organic compounds and ions. Recent research has focused on the thermal dynamics and kinetics of water molecules in solution, including experimental (infrared spectroscopy and Raman spectroscopy) and computational (Quantum Mechanics and Molecular Dynamics) approaches. The reason that water molecules are so unique, why they have such a profound influence on bio-activity, why water molecules show some anomalies compared to other small molecules, and where and how water molecules exert their influence on solutes are some of the areas under study. We studied some properties of hydrogen bond networks, and the relationship of these properties with solutes in water. Molecular dynamics simulation, followed by an analysis of “water bridges”, which represent protein-water interaction have been carried out on folded and unfolded proteins. Results suggest that the formation of transient water bridges within a certain distance helps to consolidate the protein, possibly in transition states, and may help further guide the correct folding of proteins from these transition states. This is supporting evidence that a hydrophilic interaction is the driving force of protein folding. Biological membranes are complex structures formed mostly by lipids and proteins. For this reason the lipid bilayer has received much attention, through computation and experimental studies in recent years. In this dissertation, we report results of a newly designed pH sensitive lipid MORC16, through all-atom and coarse-grained models. The results did not yield a MORC16 amphiphile which flips its conformation in response to protonation. This may be due to imperfect force field parameters for this lipid, an imperfect protonation definition, or formation of hydrogen bond does not responsible for conformation flip in our models. Despite this, some insights for future work were obtained.