Browsing by Subject "Molecular dynamics simulation"
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Item A comprehensive study of cholesterol in biomembranes using computer simulations(2011-05) Dai, Jian; Huang, Juyang; Park, Soyeun; Sanati, Mahdi; Khare, RajeshSeveral methods were applied to study the effects of cholesterol on multi-component lipid bilayers. The goal is to investigate the validity of the "Umbrella Effect" via simulations and experiments. The Umbrella Model is a hypothesis proposed based on previous structural and thermodynamical studies of lipid membranes containing cholesterol. DPPC is the most widely studied phospholipid in the simulation community. It has a large polar headgroup (which consists of a positively charged choline group and a negatively charged phosphate group), a glycerol group and two long saturated hydrocarbon chains. On the other hand, cholesterol has a relatively large carbon-ring body, compared to its small hydrophilic hydroxyl group. When a binary mixture of DPPC/cholesterol is placed in an aqueous environment, it has been suggested that cholesterol is always trying to find a “shield” to protect it from extensive contact with water, and this shield is most likely to be provided by the headgroups of phospholipids. This hypothesis is termed the “Umbrella Model”. Monte Carlo (MC) simulations will be used to study the phase transitions of multi-component lipid mixtures and molecular dynamics (MD) simulations will be used to test the Umbrella Model in direct and indirect ways, and to interpret the experimental data. Melittin is the most studied antimicrobial peptide, it can cause cell death by damaging cell membranes. Melittin interacts differently with various membrane components, such as cholesterol and negatively-charged phospholipid, both of which have been shown to reduce melittin's lytic effect against the membrane. Several model systems were constructed and simulated, different effects were observed and the possible mechanisms were discussed.Item Insight into biomolecular structure, interaction and energetics from modeling and simulation(2011-12) Zhang, Jiajing; Ren, PengyuA central goal of computational biophysics and biochemistry is to understand the behavior, interactions, and reactions of molecules, and to interpret and facilitate experimental design. The objective of this thesis research is to use the molecular modeling and simulation techniques to advance our understanding of principles in molecular structure properties, recognition and interaction at the atomic level. First, a physical molecular mechanics model is built to study the conformational properties of depsipeptide, which shows potential for engineered protein mimetics with controllable structure and function. We explore the possible kinase-substrate binding modes and the likelihood of an [alpha]-helix docking interaction within a kinase active site. Finally, efficient physical models based on a polarizable potential function are developed to describe the structural properties and calculate protein-ligand binding affinities accurately for both trypsin and matrix metalloproteinase.Item Study of lipid raft domains using computer simulation techniques(2012-05) Alwarawrah, Mohammad; Huang, Juyang; Cheng, Kelvin K.; Sanati, Mahdi; Khare, RajeshThe cholesterol condensing effect in DOPC bilayer was investigated via atomistic molecular dynamics (MD) simulation. The calculated partial-specific areas of lipids in DOPC/cholesterol lipid bilayer clearly show the condensing effect of cholesterol. The results showed that the total area of a PC/cholesterol bilayer is primarily determined by the molecular packing in the cholesterol sterol ring region. An alternative analysis of area per molecule within this region is proposed, which takes into account the cholesterol tilt angle and the practical incompressibility of cholesterol sterol rings. The new calculation shows that the majority of the area lost due to the cholesterol condensing effect is taken from PC molecules. MD simulation was also used to study the interactions between DAG, POPC, and cholesterol. Our results show that both DAG and cholesterol produce some very similar effects in POPC bilayers: increasing acyl chain order and bilayer thickness, reducing volume-per-lipid, and decreasing lateral diffusion of molecules. More significantly, DAG also produces a strong “condensing effect” in PC bilayers. In comparison, cholesterol is more effective than DAG in producing the above effects. Interestingly, our simulations also show that the largest spacing usually occurs between the first and the second nearest-neighbor PC headgroups from a DAG due to the umbrella effect. In another studies, the docking of PKCα-C1 and PKCβ-C2 domains to POPC/POPS/POG lipid bilayers were investigated using MD simulation. In the systems that contain PKCα-C1 domain, the domain only docks to a lipid bilayer that contains POG. This docking is accommodated with significant conformational changes in the PKCα-C1 domain structure. The docking of PKCα-C1 domain to lipid bilayers containing POG shows a high specificity of PKCα-C1 domain toward diacylglycerol. On the other hand, the PKCβ-C2 domain adapts a parallel configuration when it docks to the lipid bilayer in the absence of POG; however, at the presence of POG, it adapts a perpendicular configuration. Furthermore, PKCβ-C2 domain shows no significant conformational change during the docking, which agrees with the experimental studies.