Biomedical subjects

Gary S Ayton

Publications and source records attributed to Gary S Ayton.

11 recordsLinked to original sources

PubMed2006

Multiscale simulation of transmembrane proteins.

Multiscale simulation is employed to examine changes in atomistic-level protein structure due to long wavelength membrane undulations and plane stress fields. An ensemble of atomistic-level simulations of a model of a transmembrane influenza A virus M2 proton channel in a dimyristoylphosphatidylcholine (DMPC) bilayer is coupled to a corresponding mesoscopic model of a DMPC bilayer in an explicit mesoscopic solvent. Structural variations in the key proton gating His37 residues of the M2 channel are examined. Small, but distinct variations in the structure of the His37 residues are observed in both the open and closed states of the channel as a result of the coupling to mesoscopic-level membrane motions.

Dimyristoylphosphatidylcholine↗

PubMed2006

Atomistic and coarse-grained analysis of double spectrin repeat units: the molecular origins of flexibility.

Spectrin is an ubiquitous protein in metazoan cells, and its flexibility is one of the keys to maintaining cellular structure and organization. Both alpha-spectrin and beta-spectrin polypeptides consist primarily of triple coiled-coil modular repeat units, and two important factors that determine spectrin flexibility are the bending flexibility between two consecutive repeat units and the conformational flexibility of individual repeat units. Atomistic molecular dynamics (MD) simulations are used here to study double spectrin repeat units (DSRUs) from the human erythrocyte beta-spectrin (HEbeta89) and the chicken brain alpha-spectrin (CBalpha1617). From the results of MD simulations, a highly conserved Trp residue in the A-helix of most repeat units that has been suggested to be important in conferring stability to the coiled-coil structures is found not to have a significant effect on the conformational flexibility of individual repeat units. Characterization of the bending flexibility for two consecutive repeats of spectrin via atomistic simulations and coarse-grained (CG) modeling indicate that the bending flexibility is governed by the interactions between the AB-loop of the first repeat unit, the BC-loop of the second repeat unit and the linker region. Specifically, interactions between residues in these regions can lead to a strong directionality in the bending behavior of two repeat units. The biological implications of these finding are discussed.

Amino Acid Sequence↗

PubMed2006

Mesoscopic modeling of bacterial flagellar microhydrodynamics.

A particle-based hybrid method of elastic network model and smooth-particle hydrodynamics has been employed to describe the propulsion of bacterial flagella in a viscous hydrodynamic environment. The method explicitly models the two aspects of bacterial propulsion that involve flagellar flexibility and long-range hydrodynamic interaction of low-Reynolds-number flow. The model further incorporates the molecular organization of the flagellar filament at a coarse-grained level in terms of the 11 protofilaments. Each of these protofilaments is represented by a collection of material points that represent the flagellin proteins. A computational model of a single flexible helical segment representing the filament of a bacterial flagellum is presented. The propulsive dynamics and the flow fields generated by the motion of the model filament are examined. The nature of flagellar deformation and the influence of hydrodynamics in determining the shape of deformations are examined based on the helical filament.

Bacterial Physiological Phenomena↗

PubMed2006

A second generation mesoscopic lipid bilayer model: connections to field-theory descriptions of membranes and nonlocal hydrodynamics.

A new mesoscopic membrane model is developed in order to examine long-wavelength structural and dynamical membrane phenomena. Two different explicit mesoscopic solvent models are employed. The first mesoscopic solvent is denoted the big liquid oscillating blob system, which is parametrized to model water at a coarse-grained level and is motivated by a Langevin-like approach; the resulting membrane dynamics predict a solvent viscosity dependence consistent with the known viscosity of water. The second mesoscopic solvent is a Weeks-Chandler-Anderson model. Here, it is found that the correct mesoscopic hydrodynamic scaling of the membrane undulation dynamics is still preserved, although accelerated. When the behavior of the two membranes in close proximity to one another is examined, very little correlated motion is observed. However, the theoretically predicted scaling of the entropic undulation energy is confirmed, demonstrating that the entropic interaction between two membranes becomes increasingly repulsive with decreasing separation.

Algorithms↗

PubMed2005

Extending a spectrin repeat unit. I: linear force-extension response.

Nonequilibrium molecular dynamics simulations were used to calculate the elastic properties of a spectrin repeat unit. A contiguous alpha-helical linker was constructed by employing periodic boundary conditions, allowing a novel scheme for evaluating the thermodynamic force as a function of extension. By measuring the force-extension response under small extensions, spectrin was observed to behave primarily as an elastic material with a spring constant of 1700 +/- 100 pN/nm. The implications of this spring constant, in terms of the properties of the spectrin tetramer, are also discussed.

Algorithms↗

PubMed2005

Extending a spectrin repeat unit. II: rupture behavior.

A spectrin repeat unit was subject to extension using cyclic expansion nonequilibrium molecular dynamics. Periodic boundary conditions were used to examine the effects of the contiguous alpha-helical linker on the force response. The measured force-extension curve shows a linear increase in the force response when the spectrin repeat unit is extended by approximately 0.4 nm. After that point, the force response peaks and subsequently declines. The peak in the force response marks the point where the spectrin repeat unit undergoes a change in its material properties from a strongly elastic material to a mostly viscous one, on the timescales of the simulations. The force peak is also correlated with rupture of the alpha-helical linker, and is likely the event responsible for the peaks in the sawtooth-pattern force-extension curves measured by atomic force microscopy experiments. Rupture of the linker involves simultaneously breaking approximately four hydrogen bonds that maintain the alpha-helical linker. After this initial rupture, the linker undergoes simple helix-to-coil transitions as the spectrin repeat unit continues to be extended. The implications of linker rupture in the interpretation of unfolding and atomic force microscopy experiments are also discussed.

Animals↗

PubMed2005

Probing the molecular-scale lipid bilayer response to shear flow using nonequilibrium molecular dynamics.

A nonequilibrium molecular dynamics simulation of the response of dimyristoylphosphatidylcholine (DMPC) bilayers to a solvent shear flow is presented. Application of shear flow to planar, stationary DMPC bilayers results in a redistribution of the membrane density profile along the bilayer normal due to the alignment of the lipids in the direction of flow and an increase in average lipid chain length. An increase in the intermolecular and intramolecular order of the lipids in response to the shear flow is also observed. This study provides groundwork for understanding the mechanism of the full response of lipid bilayers to externally imposed solvent shear flows, beginning with the response in the absence of collective lipid motions such as undulations and bilayer flow.

Lipid Bilayers↗

PubMed2005

Multiscale coupling of mesoscopic- and atomistic-level lipid bilayer simulations.

A multiscale method is presented to bridge between the atomistic and mesoscopic membrane systems. The atomistic model in this case is the united atom dimyristoylphosphatidylcholine membrane system, although the method is completely general. Atomistic molecular dynamics provides the expansion modulus which is used to parametrize a mesoscopic elastic membrane model. The resulting elastic membrane model, including explicit mesoscopic solvent, shows appropriate static and dynamic undulation behaviors. Large membranes of approximately 100 nm in length can then be easily simulated using the mesoscopic membrane system. The critical feedback from the mesoscopic system back down to the atomistic-scale system is accomplished by bridging the stress (or surface tension) of a small region in the mesoscopic membrane to the corresponding atomistic membrane system. Because of long length-scale modes of membranes such as undulation and buckling, the local tension responds differently from the frame tension, when subjected to external perturbations. The effect of these membrane modes is shown for the stress response of a local membrane region and therefore the atomistic membrane system. In addition, certain equilibrium static and dynamic properties of stand-alone and multiscale coupled systems are presented for several different membrane sizes. Although static properties such as two-dimensional pair-correlation function and order parameters show no noticeable discrepancy for the different systems, lipid self-diffusion and the rotational relaxation of lipid dipoles have a strong dependence on the membrane size (or long-wavelength membrane motions), which is properly modeled by the present multiscale method.

Algorithms↗

PubMed2005

Coupling field theory with continuum mechanics: a simulation of domain formation in giant unilamellar vesicles.

Domain formation is modeled on the surface of giant unilamellar vesicles using a Landau field theory model for phase coexistence coupled to elastic deformation mechanics (e.g., membrane curvature). Smooth particle applied mechanics, a form of smoothed particle continuum mechanics, is used to solve either the time-dependent Landau-Ginzburg or Cahn-Hilliard free-energy models for the composition dynamics. At the same time, the underlying elastic membrane is modeled using smooth particle applied mechanics, resulting in a unified computational scheme capable of treating the response of the composition fields to arbitrary deformations of the vesicle and vice versa. The results indicate that curvature coupling, along with the field theory model for composition free energy, gives domain formations that are correlated with surface defects on the vesicle. In the case that external deformations are included, the domain structures are seen to respond to such deformations. The present simulation capability provides a significant step forward toward the simulation of realistic cellular membrane processes.

Biomechanical Phenomena↗

PubMed2004

Mesoscopic lateral diffusion in lipid bilayers.

The lateral diffusion in bilayers is modeled with a multiscale mesoscopic simulation. The methodology consists of two simulations, where the first employs atomistic models to obtain exact results for the mesoscopic model. The second simulation takes the results obtained from the first to parameterize an effective force field that is employed in a new coarse-grained model. The multiscale aspect of this scheme occurs at the point where the microscopic time-averaged results of the first simulation are employed to parameterize the second simulation that operates in a higher spatial and temporal domain. The results of both simulation schemes give quantitative information on the details associated with lipid lateral diffusion.

Cholesterol↗

PubMed2004

A new perspective on the coarse-grained dynamics of fluids.

A computational methodology is presented that is designed to model, at a coarse-grained level, the mesoscale dynamics of fluids and potentially other forms of soft matter. Within a molecular dynamics simulation, "ghost" particles of a specific size, corresponding to the fundamental length-scale of coarse-graining, are used as micro-probes designed to respond to local mesoscale fluid flows and stress gradients. A subsequent coarse-grained model is then developed that incorporates both the coarse-grained mesoscale dynamics and isothermal compressibility of the original microscopic system. The method is applied to water and methanol. A contrast with dissipative particle dynamics (DPD) is also presented.

Colloids↗