Dissertation > Excellent graduate degree dissertation topics show

Molecular Dynamics Simulation for Two Kinds of Estrogen Receptors Binding with Inhibitors

Author: LiLongFei
Tutor: ZhangShaoLong
School: Shandong Normal University
Course: Atomic and Molecular Physics
Keywords: Molecular dynamics simulation Binding free energy ER estrogen Molecular mechanics , Poisson - Boltzmann solvent accessible surface area (MM-PBSA)
CLC: Q57
Type: Master's thesis
Year: 2011
Downloads: 53
Quote: 0
Read: Download Dissertation

Abstract


Molecular dynamics (molecular dynamics, MD) simulations to study the structure and properties of biological molecules important tool. Having a large number of atoms interacting molecular systems, molecular dynamics represents a potential function interaction between atoms, each atom that the system obey Newton's equation of motion, on the system by solving the kinetic equations of each atom obtained in the phase space of a system of evolutionary tracks, then use the methods of statistical mechanics to get information about the system, such as the energy density. Just know the interaction potential function, molecular dynamics can be simulated with complex many-body interactions of biological molecules movement. Molecular dynamics simulation results help to understand the structure and function of biological molecules. Hybrid quantum classical methods (Hybrid QM / MM) includes both the accuracy of quantum mechanics, and the use of molecular mechanics efficiency. Important for the system, the part related to changes in the quantum chemical mechanical method to handle. As for the secondary system, is not directly related to the use of chemically changed part way to describe the molecular mechanics. This will not only more accurately reflect changes in the electronic structure (relative to the pure molecular mechanics force field method), but also makes the computational overhead is not using full quantum mechanical methods so great. QM / MM methods to study protein macromolecules such as QM theory used mainly semi-empirical methods, density functional theory. Binding free energy calculations for the study of protein inhibitors and the interaction between the mechanism is very important. Accurately predict the free energy can better understand the structure and function of biological macromolecules relationship for provide the basis for rational drug design. Molecular Mechanics / Poisson - Boltzmann solvent accessible surface area (molecular mechanics / Poisson-Boltzman surface area, MM-PBSA) method is the application of a wide empirical equation based on the free energy calculation methods. The negative free energy determines the possibility of combining, which determines the extent of reaction. Estrogens (estrogens response) in the female reproductive system development and physiological processes play a key role in controlling blood calcium levels and maintain bone density also has an important role. Estrogen and estrogen receptors by (estrogen receptor, ER) play a role in the interaction between. ERα and ERβ have now found two kinds of estrogen receptors, estrogen receptors by two kinds of the crystal structure of the inhibitor binding a large number of studies have found, ERα and ERβ in the respective active region of the structure is very similar, but in the binding pocket There are two nearby residues different, ERα in the Leu384 and Met421 in ERβ, respectively, corresponding to Met336 and Ile373, these small differences lead to ERα and ERβ with different mechanisms of action inhibitors, inhibitors of both receptors and mechanisms highly selective inhibitor of the design is important. In this paper, ERα and ERβ two composite system was aqueous environment under 12ns molecular dynamics simulations to study the two systems during the simulation conformational changes. With MM-PBSA method two estrogen receptors and inhibitors of the binding free energy of 244 were -30.11 kJ / mol and -37.87 kJ / mol, indicates that ERβ system inhibitors and protein easier to combine to form a composite more stable structure. ERα Met421 side chain atoms of the inhibitor effect of electrostatic repulsion between the pocket around the active residues of a conformation change, resulting in the active region with a hole becomes large, so that ERα and lower affinity inhibitors. This paper also ERα and ERβ two composite system was under 1ns aqueous environment of QM / MM simulations. Through molecular dynamics calculations and the results of a comparative study can be found, QM / MM method to calculate the results more precise. Thesis is divided into four chapters: The first chapter is the introduction section, a brief introduction to the estrogen receptor (ER) structure, function and estrogen receptor inhibitor research development; second chapter of the theory and methods section, introduction the use of molecular mechanics methods, mixed classical quantum mechanics, molecular dynamics simulations and free energy calculation methods; chapter describes the molecular dynamics simulation on estrogen receptors ERα and ERβ system for molecular dynamics studies process; fourth chapter studies the molecular dynamics process of ERα and ERβ system conformational changes; fifth chapter with QM / MM methods for two estrogen receptors and inhibitors combined system was simulated.

Related Dissertations

  1. Hydrophilic structure of different types of surface -modified polyurethane material and coagulation 12 factor nine peptide fragments,and fibrinogen P1 fragment of computer simulation of the interaction,O631.3
  2. Molecular Dynamics Simulations of Temperature Effects on Pt/Au Heteroepitaxial Growth,O484.1
  3. Molecular Dynamics Simulations of Structural Relaxation of Two-dimensional Lattice Mismatch Epitaxial Aluminum Thin Film,O484.1
  4. Intvestgation of Ligand Channels and Cooperativity Mechanism in Cytochrome P450s,Q559.9
  5. Different electrical properties of carbon nanotubes covalently modified FAD molecular dynamics simulation,TB383.1
  6. Lead laser ablation pit modeling and single pulse laser-induced breakdown spectroscopy,TN247
  7. Conduction Study Through Carbon Nanotubes as Channels of Salt and Water,TB383.1
  8. Molecular Mechanism Study of the Structure Stability of Amyloid Protein by Peptide Inhibitors,O629.73
  9. Investigation on Structure of Element Semiconductor Material Si and Ge Melt,TN304.1
  10. Molecular Dynamics Simulations of Folding of Saturated Polyalanine Based on the Rigidbody Dynamics Model,Q51
  11. Molecular Dynamics Simulations of Organic Solvent Based on Coarse-Grained Model,O561
  12. The Simulation on Mechanical Property of Carbon Nanotube Torsional Deformation and Thermal Stability of Oscillatingtube,TB383.1
  13. The Dynamics of Movements and Reconstructions of Defect in Single-walled Carbon Nanotube Junction,TB383.1
  14. Molecular Simulation Studies in Discovery of HIV-1 and H5N1 Inhibitors,R914
  15. Study on the Mechanism of PIP2 Regulating Three Kir Channels,Q26
  16. POSS modified microscopic model dental composite resin Establishment and molecular modeling studies,TB332
  17. Studies on Water Trimers in Terms of ab initio and ABEEM/MM Methods and Review of the Methods of Calculating Binding Free Energies of Ligands and Receptors,O631.3
  18. Preparation of Zinc Oxide Thin Films with Preferential Orientation and the Growth Process of Oxide Thin Films Simulated by Molecular Dynamics,O614.241
  19. Research on Affect Mechanism of Rotating Electromagnetic Effect to Structure and Dynamic Property of Seawater,P747
  20. The Phenomena of Discharge in Supercritical Carbon Dioxide,O461
  21. Nano-Cutting Surface Quality for Single Crystal Silicon and Molecular Dynamics Simulation,TG501

CLC: > Biological Sciences > Biochemistry > Hormone
© 2012 www.DissertationTopic.Net  Mobile