|
|
Molecular dynamics simulations of biomolecules
Naništa, Ján ; Barvík, Ivan (advisor) ; Bok, Jiří (referee)
This study deals with classical molecular dynamics simulations of time evolution of a biomolecular system. The simulated system consists of the D3 GPCR membrane receptor for dopamine surrounded by a cell membrane and covered with water molecules and ions. The aim was to analyze the ability of Eticlopride to bind into the active site of the GPCR receptor.
|
|
| |
|
|
Photocontrolled Biomolecules
Planer, Jakub ; Bartošík, Miroslav (referee) ; Vácha,, Robert (referee) ; Kulhánek, Petr (advisor)
This work is focused on molecular dynamics simulations of artificial photosensitive ion channel and AFM probe. To assemble this ion channel, DFT methods were employed for reparametrization of the GAFF force field describing the bridged azobenzene, which was used as a light controlled molecular switch. We proved by molecular dynamics simulations that newly developed parameters correctly describe behavior of assembled model of ion channel in a lipid bilayer. We also constructed a model of AFM probe and observed formation of water meniscus between the AFM probe and surface, both made of -quartz, by employing molecular dynamics simulations. A contribution of this work is the set of new parameters extending GAFF force field for description of the bridged azobenzene. We also verified functionality of ion channel model and model of AFM probe, which can be used for the further water meniscus studies.
|
|
|
Molecular simulation study of aqueous solutions of alifatic alcohols
Peštuka, Martin ; Žídek, Jan (referee) ; Janeček, Jiří (advisor)
The aim of this bachelor thesis was to carry out set of molecular dynamic simulations of aqueous solutions of aliphatic alcohols in infinite attenuation. In order to work with molecular dynamic simulations it was necessary to become familiar with the program equipment to perform molecular dynamic simulations and analyze the results. Within the work the basic simulation boxes contained 300, 400, 500 and 1000 water molecules and one molecule of aliphatic alcohol. From the simulated trajectories we evaluated the volume change associated with the insertion of one particle of alcohol and the radial distribution functions around the molecule of solute. The results were compared with experimental data.
|
|
|
Deformation mechanisms in crystals by means of molecular dynamics
Lamberský, Vojtěch ; Grepl, Robert (referee) ; Černý, Miroslav (advisor)
This work deals with molecular dynamics modeling of processes in condensed matter on atomic level. The physical principles used to predict motion of atom or molecule groups are described in the retrieval part. Then follows a description of the EAM method, ways how to parallelize computing on many processors and how perform calculation optimizing. Finally, we perform a theoretical tensile strength computation using Lammps program.
|
|
|
Study of interactions of organic matter and its components via molecular dynamics
BARVÍKOVÁ, Hana
Humic acids and humates are principal components of humic substances major organic constituents of soil, peat, coal and water around the world. I was involved in research into molecular dynamics simulations of interactions of quartz surfaces with aqueous solutions of ions and small organic molecules representing basic building blocks of larger biomolecules and functional groups of organic matter. We studied interactions of molecules with surfaces for a set of surface charge densities corresponding to the experimentally or environmentally relevant ranges of pH values employing molecular mechanics, molecular dynamics and ab initio techniques. Simulated quartz surfaces covered the range of surface charge densities 0.00, -0.03, -0.06 and -0.12 C-m-2, approximately corresponding to pH values 4.5, 7.5, 9.5 and 11. As model molecules, benzoic acid, phenol, o-salicylic acid and their conjugated bases were chosen. My task was to prepare topologies and parametric models of selected organic matter basic building blocks organic molecules. I focused on studying interactions of these molecules in an aqueous environment with mineral surface quartz. The aim was to process simulation results and analyse conformations of the adsorption complexes and their thermodynamic properties such as interaction energies, free energies and adsorption geometries.
|
|
|
Molecular dynamics as a tool to study biological systems
SOVOVÁ, Žofie
Molecular dynamics simulations are a theoretical method enabling to trace the movement of atoms within a system. The system studied is usually treated on the atomistic level, however its overall properties can be also described satisfactory if several atoms are handled as one particle (coarse-grained molecular dynamics). This thesis presents molecular modeling and (coarse-grained) molecular dynamics as tools for the description of different biologically relevant systems. The coarse-grained force field parameters had to be developed prior to characterization of the thylakoid membrane from cyanobacterium Synechocystis PCC6803. Two different compositions of the membrane were studied in order to reveal differences in their behavior. The PsbI subunit of photosystem II was embedded into the thylakoid membrane and its behavior, both as an isolated protein and as a cluster of several units, was described. The last system examined was the C-type lectin-like domain of NKR-P1, a surface receptor of natural killer cells. Attention was payed to its structural characterization.
|
|
|
Computer simulation of interactions of molecules with mineral surfaces
BARVÍKOVÁ, Hana
This thesis is focused on molecular dynamics, modelling interactions and their simulation. One of the tasks was to familiarize with GROMACS, a molecular dynamics simulation software. This work also introduces the basics of molecular dynamics and modelling interactions of organic molecules with mineral surfaces. The aim of the thesis was to solve model tasks in GROMACS and analyze the output results. The thesis describes some of the most important file formats and utilities that are needed for working with GROMACS and the use of both the formats and the utilities. In this program, I built up several systems consisting of combinations of organic molecules such as benzoic acid, phenol, salicylic acid and their conjugate bases with mineral surfaces (quartz crystal) of different surface charge density. Furthermore I analyzed the results of these simulations, behaviour of the structures and adsorption geometries and interaction energies within these systems. The thesis might also serve as a quick introduction and familiarization with GROMACS with emphasis on simulations and analysis of systems with planar interfaces. Within the MetaCentrum Project I worked on the Hermes Computer Cluster belonging to the Faculty of Science at the University of South Bohemia.
|
|
|
Computational Investigations of Biomolecular Systems and Comparison with Experiments in Various Environmental Conditions
KHABIRI, Morteza
Computational methods were used to study two different types of biological systems. The first study is related to the effect of three different organic solvents (formamide, acetone and isopropanol) on the structure and behavior of three globular proteins. These enzymes belong to the haloalkane dehalogenase family: DhaA, LinB, and DbjA. Moreover, the effect of mutation in the presence of DMSO was also investigated in two variants of DhaA; DhaA57 (L95V+A172V) and DhaA80 (Thr148Leu+Gly171Gln+Ala172Val+Cys176Phe). The simulation results showed that except for DhaA80, organic solvents entered the active site and influence its hydration. Not only the active site but also the enzyme?s hydration shell is influenced by organic molecules. The results showed that the water molecules are stripped out from the enzyme surfaces. It seems that the dual nature of organic molecules makes them favorable to solvate the enzymes. Radial Distribution Function (RDF) of the different parts of each organic molecule reveals that the behavior of each organic solvent in the vicinity of hydrophobic surfaces is similar to their behavior at the air-water interface. Structural analysis of root-mean-square-deviations (RMSD) and B-factors reveals that the flexibility of the enzymes decreased in the presence of most organic solvents, mainly in the CAP domain. Changes of other structural properties like radius of gyration and total solvent accessible surface areas are minimal. DbjA exists as a dimer and is more influenced by organic molecules. They penetrate to the amino acid network between monomers and influence their motion. The second study is the interaction of voltage-gated potassium channel Kv1.3 wild type and its mutants (Kv1.3_V388C, Kv1.3_V388C_H399T) with scorpion toxin (ChTX). Since there is no structure for Kv1.3, 94% sequence identity with Kv1.2 structure was used to make a homology model based on the Kv1.2 structure. MD structural analyses reveal that mutation of V388C changes the stability of selectivity filter by interrupting the amino acid network interactions behind the selectivity filter. The interaction of ChTX is also affected by the single mutant. ChTX is able to block wild type and double mutant channels but cannot occlude the pore entirely. Introducing the second point mutation H399T in the pore region reverts the structural changes back to the wild type. These results are entirely consistent with experimental results. Additionally, the binding energy of ChTX with the wild type mKv1.3 was investigated by the potential of mean force method, in the presence and absence of KCl solution. The results both in experiment and simulation show that, even though the unbinding process and dissociation rate is changing in the present of K+ ions, the binding energy is independent of K+ concentration. All together, the combination of computer simulations together with experiments provides new knowledge about channel-toxin interactions which could be helpful for drug design.
|
|
|
Structural analysis of extrinsic proteins from the oxygen-evolving complex of photosystem II from higher plants
KOHOUTOVÁ, Jaroslava
All life on earth depends mainly on the presence of oxygen. Largest producers of oxygen are green plants, cyanobacteria and algae. Oxygen is released from the oxygenevolving complex of photosystem II during photosynthesis and it is used in cellular respiration of all life complexes. The oxygen-evolving complex of photosystem II has the same function in each photosynthetic organism, but it has a different composition and organization of extrinsic proteins; only PsbO protein is ubiquitous in all known oxyphototrophs. Until now only low resolution electron microscopy structural models of plant PSII and crystal structures of cyanobacterial PSII are available. Higher plant extrinsic proteins (PsbP, PsbQ and PsbR) are structurally unrelated, non-homologues to the cyanobacterial extrinsic proteins (PsbO, PsbU and PsbV) and this is the reason why it is not possible to predict arrangement of these proteins on the lumenal site of higher plant PSII. Recently, models differ mainly in the structure of the oxygen-evolving complex, which could be resolved by determination of the exact binding sites for extrinsic proteins. An other question evolves: if the difference in the oxygen-evolving complex composition is the result of evolution or adaptation of photosynthetic organisms to their environment. Structural knowledge of extrinsic proteins that could help to resolve the location and subsequently the function of extrinsic proteins is still incomplete. From this case,structural analysis, interactions and probably arrangement of proteins PsbP and PsbQ was studied and is described in detail in this thesis.
|
guest ::
