Study The Reaction Mechanism Of Organic Molecules/ Protein Using Molecular Mechanics/Dynamics

With the rapid development of computer science, computer molecular modeling plays an increasingly important role in scientific research. With further research and development, molecular modeling techniques expand from the quantum chemistry simulation methods to molecular mechanics simulation methods and molecular dynamics simulations which are of high computational efficiency. We utilize molecular mechanics simulation methods and molecular dynamics simulations to study self-assembled organic molecules on graphite and protein molecules, respectively. In addition, we also provide theoretical assistance to experiments by explaining mechanism underlying the chemical reactions.Self-assembled Tri-alkoxylated benzene(B-OCn) shows a variety of adlayer patterns on graphite depending on the concentration in solution. One porous and two densely linear 2D patterns(zigzag and stripe) are found as the concentration increasing. We have inferred the theoretical models of these phases from the STM pictures and performed molecular mechanical studies and theoretical calculations to investigate the thermodynamic properties of these three patterns. It is found that Van der Waals interactions resorting to interdigitation of alkyl chains dominate the self-assembled patterns, with a significant contribution to the total potential energy of the systems. The values of enthalpy and entropy change of releasing a B-OCn molecule from HOPG to solvent conformed that porous structure, with less molecular density per unit aera, is enthalpy favorable, and zigzag is entropy favorable structure, with denser molecular density. In addition, we roughly estimate the free energies of these systems, which are used to judge the trend of the transitions among these sequential phases. At last, we have taken co-adsorbed solvent molecules into consideration in porous pattern. And the significance of solvent molecules can be easily distinguished from their contributions to the enthalpy and entropy changes, which can help choose suitable solvent in experiment.Respiratory complex I, the biggest enzyme of respiratory chain, plays a key role in energy production by the mitochondrial respiratory chain and has been implicated in many human neurodegenerative diseases. Recently, the crystal structure of respiratory complex I is reported. We perform 50 ns molecular dynamics(MD) simulations on the membrane domain of respiratory complex I under two hypothetical states(oxidized state and reduced state). We find that, the density of water molecules in the trans-membrane domain under reduced state is bigger than that under oxidized state. The connecting state than that under oxidized state, causing more internal water molecules and facilitating the proton conduction. The conformational changes of helix HL and the crucial charged residue Glu in TM5 play key roles in the mechanism of proton translocation. Our results illustrate the dynamic behavior and the potential mechanism of respiratory complex I, which provides the structural basis for drug design of respiratory complex I.