Browsing by Subject "Molecular dynamics simulations"

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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, David
The 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.
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.
The early translocation of anthrax lethal factor by atomically detailed simulations and Milestoning theory
(2021-08-06) Ma, Piao, Ph. D.; Elber, Ron; Makarov, Dmitrii E.; Matouschek, Andreas; Thirumalai, Devarajan; Ren, Pengyu
The pathogenesis of the anthrax toxin requires the translocation of the lethal factor (LF) or the edema factor (EF) from the endosome to the cytosol though the anthrax channel. The channel is formed by protective antigen (PA) proteins. In this dissertation, we are interested in the translocation of LF through the anthrax channel. The unstructured N-terminal segment (LFN) of LF consists of 30 residues and is leading the translocation event. A critical barrier for the translocation across the channel is the ϕ clamp which consists of seven phenylalanine (F) residues in a ring. It is the narrowest part of the channel and is considered the dividing line between the endosome and the cytosol solutions. We use atomically detailed simulations to study the translocation process. The solvated system (the channel and LF) contains about 680,000 atoms. Therefore, the computational costs of straightforward molecular dynamics simulations are significant. To facilitate the atomically detailed calculations we use the method of Milestoning. Milestoning simulate the overall process using short trajectories between interfaces called milestones. The information from the short trajectories, which are computed efficiently, is used to build a stochastic model for the entire process. LFN modifies its protonation state depending on the pH. Positively charged LFN permeates more easily through the ϕ clamp compared to a less charged LFN. This preference is explained by the high concentration of negatively charged residues at the inner side of the anthrax channel. The electrostatic interactions provide the driving force for the permeation of LFN. In vivo systems, the positively charged state is supported by the low pH in the endosome. Once LFN passes the ϕ clamp, the N-terminal peptide chain is fully stretched and exerts a force on the rest of the protein. It assists the unfolding of the rest of the protein in preparation for a complete translocation. Mutations of the F427 residues at the ϕ clamp impact the translocation.
Theoretical and numerical study on adhesive interactions between graphene and substrate
(2018-06-14) Wang, Peng, Ph. D.; Huang, Rui, Ph. D. in civil and environmental engineering.; Liechti, Kenneth M; Landis, Chad M; Ravi-Chandar, Krishnaswa; Ren, Pengyu
This dissertation presents a set of theoretical and numerical studies on adhesive interactions between monolayer graphene membranes and their substrates. Both continuum mechanics models and molecular dynamics simulations are developed to investigate deformation of graphene membranes depending on the adhesive interactions with the substrates. First, a numerical study on snap transitions of gas-filled graphene blisters is presented, based on a continuum model combining a nonlinear plate theory with a nonlinear traction–separation relation. The numerical results may be used in conjunction with experiments for quantitative characterization of the interfacial properties of graphene and other two-dimensional (2D) membrane materials. Next, a statistical mechanics analysis on thermal rippling of monolayer graphene supported on a rigid substrate is presented and compared with molecular dynamics simulations to reveal the entropic effects of thermal rippling on van der Waals interactions between graphene and the substrate. While the amplitude of thermal rippling is reduced by the adhesive interactions, the entropic contribution of thermal rippling leads to an effective repulsion, thus reducing the effective adhesion. Moreover, the effect of a biaxial pre-strain in graphene is considered, and a buckling instability is predicted at a critical compressive strain that depends on both the temperature and the adhesive interactions. This motivates a systematic study on morphological transitions of monolayer graphene on a substrate under uniaxial compressive strain, from rippling to wrinkling/buckling and to folding. The presence of water at the interface has significant influence on the adhesive interactions between graphene and its substrate. Molecular dynamics simulations are performed to study the interactions between graphene and a wet substrate that is covered by a thin layer of water. Four stages of the traction-separation relations are identified and they are analyzed approximately by simple continuum models. When the thickness of water layer is below 1 nm, the water molecules form discrete monolayer or bilayer structures, leading to different traction-separation behaviors. Finally, with a finite number of water molecules trapped between a monolayer graphene and its substrate, water-filled graphene blisters form spontaneously. Based on molecular dynamics simulations and a simple theoretical model, the work of adhesion for the graphene/substrate interface may be estimated by measuring the aspect ratios of the graphene blisters. Unlike gas-filled graphene blisters in previous studies, the shape and size of the water-filled graphene blister depend on the wetting properties of graphene and the substrate. The results on wet adhesion and water-filled blisters can be readily extended to other 2D materials.