Computer simulation study on protein structure using molecular dynamics and Monte Carlo method

Abstract

Chapter 1. Computer Simulation is useful tool investigating the physical properties of various molecular systems, including biomolecules, polymers, organic molecules, and materials, which are very difficult to approach by experiment. We will summarize the fundamentals on Molecular Dynamics and Monte Carlo Procedure, main part of the molecular simulation. Chapter 2. We have performed NPT molecular dynamics simulations (Langevin Piston Method) on two type of solvated proteins - "denaturation-unfavorable" protein (insulin) and "denaturation-favorable protein" (ribonuclease A) at high pressure (from 1 bar up to 20 kbar). The method is based on the extended system formalism introduced by Andersen, where the deterministic equations of motion for the piston degree of freedom are replaced by Langevin equation. We report the structural changes of proteins (ribonuclease A and insulin) and water molecules through radius of gyration, solvent accessible surface area, hydrogen bond pattern, and the topology of water clusters connected by the hydrogen bonded circular network. The solvent accessibility of ribonuclease A are mainly decreased by hydrophilic residues rather than hydrophobic residues under high pressure. From the results of hydrogen bond analysis, we have found that α-helix is more stable than β-sheet under high pressure. In addition, from the analysis of the water cluster, we have observed that for ribonuclease A, 5-membered ring structure is more favorable than 6-membered ring as higher pressure. However, for insulin, the ratio of 5 to 6-ring is constant over the pressure ranges, for which we have performed MD simulation. This indicates that the water structure around insulin does not change under high pressure Chapter 3. A new Monte Carlo sampling scheme, namely the Modified Valley Restrained Monte Carlo procedure, is used to obtain the global energy minimum conformations for polypeptides, such as Met-enkephalin and Melittin. For each peptide, we found close ag...