Browsing by Subject "Molecular dynamics simulations"
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Item Direct measurement of membrane dipole field in complex model membranes via vibrational stark effect spectroscopy coupled with molecular dynamics simulations(2016-08) Shrestha, Rebika; Webb, Lauren J.; Elber, Ron; Gordon, Vernita; Stachowiak, Jeanne; Vanden Bout, DavidThe heterogeneous composition of a biological membrane creates a complex electrostatic environment that regulates membrane structure and function. In this work, we investigated the magnitude of the membrane dipole field, Fd, located entirely within the low dielectric membrane interior as a function of membrane composition complexity. We directly measured Fd in vesicle model membrane composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) using vibrational Stark effect (VSE) shifts of nitrile oscillators systematically placed along the membrane interior coupled with extensive Molecular Dynamics (MD) simulations. We calculated the absolute magnitude of Fd in DMPC vesicles to be 8-11 MV/cm, at the high end of the range provided in literature. We increased the complexity of the membrane composition by intercalating cholesterol molecule at a wide range of concentration (0- 40 mol%) and found that cholesterol increased Fd at low concentration (~10 mol%), and decreased Fd at higher concentration (>10 mol%). This result, when compared to lipid bilayers containing a cholesterol derivative, 6-ketocholestanol (6-kc) that differs from cholesterol by only a ketone functional group, was strikingly different. Using the spectral line widths obtained from Fourier-transform infrared spectroscopy experiments and molecular dynamic simulations on model lipid-sterol bilayers, we propose that the membrane dipole field is greatly correlated to the local membrane structure and organization regulated by the sterols in the bilayer. We propose that at low concentrations, cholesterol increases dipole field by increasing packing density of disordered lipids, cholesterol and their associated hydrogen bonded water dipoles whereas at high concentrations, the sterol decreases the field by forming liquid ordered state enriched in cholesterol, thus spacing out phospholipids along with water dipoles. 6-kc, on the other hand, is homogeneously distributed and increases hydrogen bonding with water dipoles via two polar groups on its sterol ring, thus never promoting ordered domain and increasing the dipole field monotonously. We also investigated the translocation mechanism of positively, negatively and zwitterionic charged tryptophan molecules through a phospholipid bilayer using time dependent fluorescence spectroscopy and atomically detailed simulations. Both experiment and simulation reproduced the qualitative trend and suggested that the fastest permeation occurred for positively charged tryptophan. Molecular dynamics simulations revealed that the translocation mechanism was assisted by a local defect and the permeation process was insignificantly influenced by the long-range electrostatic interactions, such as the membrane dipole potential.Item Experimental and computation study of protein interactions with lipid nanodomains(2013-05) Qiu, Liming; Cheng, Kelvin K.; Vaughn, Mark W.; Sanati, Mahdi; Khare, Rajesh; Quitevis, Edward L.Protein lipid interactions are significantly relevant to understanding of a wide variety of biological phenomena in general. In particular, human beta-amyloid protein is closely related to the pathogenesis of Alzheimer's disease. Due to its high propensity to self-aggregate, beta-amyloid protein is difficult to study with experiments. Molecular dynamics simulations is capable of providing atomistic details of the protein lipid interactions; therefore, is an important theoretical tool to investigate these subtle interactions and offer insights to the pathogenesis of Alzheimer's disease. In this dissertation, I studies the protein lipid interactions with several systems with different lipid composition and protein conformations. I developed computational tools to quantitatively analyze lipid perturbations due to protein interactions, since it is commonly believed that the neurotoxicity of beta-amyloid protein is through perturbation of the lipid membrane. I discovered that for the case of a beta-amyloid dimer on the surface of lipid bilayers, the perturbation effect of protein is correlated to the degree of disorder of the protein in term of its secondary structure. Meanwhile, for a system where a beta-amyloid protein was partially inserted into the bilayer, the protein insertion rate was regulated by both the secondary structure of the protein and the lipid environment. Especially, a scaling relation between the insertion rate and degree of disorder was found. Even though molecular dynamics simulations is a powerful tool in studying atomistic protein lipid interactions, it is not efficient in sampling the free energy landscape of the system; hence results are biased by the initial structure of the system. I developed a multiscale molecular simulation scheme to increase the efficiency in free energy landscape sampling by switching the system between different spatial resolutions, i.e., atomistic and coarse-grain representations of the system. Using this method, I discovered a novel protein lipid orientation, which has implications in understanding the biochemical pathway of the protein as well as developing therapeutic interventions. Finally, I also developed a Monte Carlo method to estimate molecule volumes accurate to atomistic scale. This method is directly applicable to lipid membrane system with heterogeneous components including proteins; it is a useful tool for not only investigating protein lipid interactions but also calibration of force field parameters for classical molecular dynamics simulations.Item Molecular dynamics simulations of multiple Ag nanoclusters deposition on a substrate(2014-05) Boumerdassi, Nawel; Becker, Michael F.Ag thin and thick films have been experimentally deposited using a technique called Laser Ablation of a Microparticle Aerosol (LAMA). This technique is based on a supersonic jet accelerating NPs of a few nm diameter up to 1000 m/s and operating at room temperature. The deposited films have experimentally demonstrated interesting properties such as dense growth with good adherence on the substrate. Aerosol feed rates have been fixed to 10 mg/h which corresponds to rate depositions of 10¹⁰ to 10¹¹ NPs/s/cm². In order to model this deposition technique and possibly be able to predict the morphology and structure of deposited films using computational methods, we have designed MD programs simulating the depositions of several Ag nanoclusters onto a substrate at a fixed temperature (300 K). The variation of parameters such as cluster size, cluster impact energy, and deposition rate has influenced the morphology and structure of the deposited films. Cluster diameters have been set to 3 nm or 5 nm, cluster velocities set to 200 m/s (0.022 eV/atom), 400 m/s (0.069 eV/ atom), or 800 m/s (0.358 eV/atom), and the deposition rate adjusted to ensure relaxation times between impactions of 5 ps to 20 ps. The evolution of deposited film density, adherence, and crystal arrangement has been analyzed with the variation of the aforementioned parameters. The highest cluster velocities have enabled the deposition of smoother, denser, and more adherent films. NCs with an initial velocity of 200 m/s have shown ratios of flattening equal to 50 % as opposed to 85% flattening for NCs deposited at 800 m/s. These observations have enabled us to draw qualitative conclusions on the film density The deposited films are less porous when the cluster impaction velocity increases. Atomic mixing between substrate and impacted NC atoms increased with increasing deposition velocity, which can perhaps be correlated to an increase of adherence, assuming that more mixing will create stronger molecular binding in the cluster-substrate interaction. Finally, complete epitaxial growth was observed for the highest impaction velocities only, which indicates that recrystalization can occur for this range of impact energies (0.3 eV/atom - 0.5 eV/atom). Although experimental results have given more quantitative data on film density and sticking ratios, they agree with our modeling, and this comparison allows us to validate our MD simulations. However, some limitations have been faced, mainly because of long computing time requirements that a single laptop computer has not been able to support.Item Molecular dynamics: Hooke-Lennard-Jones hybrid method(2012-05) Blackwell, Morgan; Smith, Philip W.; Long, KevinIn this thesis we apply Hookes law and the Lennard-Jones potential together forming a hybrid potential energy function to model atomic interaction. These molecular dynamics simulations are then implemented in Matlab. For each simulation, we construct a cubic lattice of particles set at an equilibrium distance apart with most particles given an initial random velocity. The simulations are representative of generic solids. We observe how the system moves through time as the particles interact with one another. We are interested in investigating the e ciency of our Matlab implementation, evaluating the accuracy of the Runge-Kutta integration algorithm being used, and assessing the appropriateness of this hybrid potential to model cubic lattices. This paper discusses the advantages and disadvantages of applying the fourth order Runge-Kutta (RK4) quadrature method to Newtons second law of motion in order to produce the trajectories of each particle in the system as they vary with time. Knowing that the RK4 method will not conserve energy, we observe how large our simulations can get before it produces too much error resulting in the loss or gain of energy. We also report on the run time performance of the code and suggest future improvements.