Molecular Engineering of Peptides

AbstractDeeper understanding of the role of short peptides in lipid layers has revealed potential applications for rationally designed synthetic replacements. A recent report illustrates the succesful design of a peptoid mimic of SP-C, a protein linked to respiratory distress syndrome

Looking inside the entanglement “tube” using molecular dynamics simulations

For 30 years, the dynamics of entangled polymers have been explained using the phenomenological “tube” model, where the “tube” represents the confining effects of surrounding chains, but the tube properties, such as its length and diameter, could only be inferred indirectly by fitting the tube model to rheological data. Now, however, molecular simulations are allowing these properties to be directly computed. The computational advances in molecular dynamics and related methods that have made this possible are here reviewed. In addition, it is discussed how new findings, such as an apparent time dependence of the tube diameter and direct observation of “hopping” of branch points along the tube, are helping to refine the tube model. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 3240–3248, 2007Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57371/1/21332_ftp.pd

Brownian dynamics simulations of flexible polymers with spring–spring repulsions

We develop a method which incorporates spring–spring repulsions into Brownian dynamics simulations of flexible polymers. The distance of closest approach between two springs is computed, and a repulsive force is then applied based on this distance. Repulsive potentials of the exponential and power-law forms are considered. We demonstrate that our method is capable of accounting for excluded-volume effects in start-up of extensional flow. Equilibrium simulations indicate that spring-spring repulsions can be used to prevent the passage of two springs through each other, and thus maintain the topological integrity of polymer molecules. The method developed here is expected to be useful for simulating entanglement phenomena in both single and multichain systems. © 2001 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69579/2/JCPSA6-114-15-6937-1.pd

Cation and anion transport through hydrophilic pores in lipid bilayers

To understand the origin of transmembrane potentials, formation of transient pores, and the movement of anions and cations across lipid membranes, we have performed systematic atomistic molecular dynamics simulations of palmitoyl-oleoyl-phosphatidylcholine (POPC) lipids. A double bilayer setup was employed and different transmembrane potentials were generated by varying the anion (Cl−)(Cl−) and cation (Na+)(Na+) concentrations in the two water compartments. A transmembrane potential of ∼ 350 mV∼350mV was thereby generated per bilayer for a unit charge imbalance. For transmembrane potential differences of up to ∼ 1.4 V∼1.4V, the bilayers were stable, over the time scale of the simulations (10–50 ns)(10–50ns). At larger imposed potential differences, one of the two bilayers breaks down through formation of a water pore, leading to both anion and cation translocations through the pore. The anions typically have a short residence time inside the pore, while the cations show a wider range of residence times depending on whether they bind to a lipid molecule or not. Over the time scale of the simulations, we do not observe the discharge of the entire potential difference, nor do we observe pore closing, although we observe that the size of the pore decreases as more ions translocate. We also observed a rare lipid flip-flop, in which a lipid molecule translocated from one bilayer leaflet to the opposite leaflet, assisted by the water pore.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87872/2/074901_1.pd

Hydrodynamic bifurcation in electro-osmotically driven periodic flows

In this paper we report a novel inertial instability that occurs in electro-osmotically driven channel flows. We assume that the charge motion under the influence of an externally applied electric field is confined to a small vicinity of the channel walls that, effectively, drives a bulk flow through a prescribed slip velocity at the boundaries. Here, we study spatially-periodic wall velocity modulations in a two-dimensional straight channel numerically. At low slip velocities, the bulk flow consists of a set of vortices along each wall that are left-right symmetric, while at sufficiently high slip velocities, this flow loses its stability though a supercritical bifurcation. Surprisingly, the new flow state that bifurcates from a left-right symmetric base flow has a rather strong mean component along the channel, which is similar to pressure-driven velocity profiles. The instability sets in at rather small Reynolds numbers of about 20-30, and we discuss its potential applications in microfluidic devices.Comment: 13 pages, 6 figure

Brownian dynamics simulations with stiff finitely extensible nonlinear elastic-Fraenkel springs as approximations to rods in bead-rod models

A very stiff finitely extensible nonlinear elastic (FENE)-Fraenkel spring is proposed to replace the rigid rod in the bead-rod model. This allows the adoption of a fast predictor-corrector method so that large time steps can be taken in Brownian dynamics (BD) simulations without over- or understretching the stiff springs. In contrast to the simple bead-rod model, BD simulations with beads and FENE-Fraenkel (FF) springs yield a random-walk configuration at equilibrium. We compare the simulation results of the free-draining bead-FF-spring model with those for the bead-rod model in relaxation, start-up of uniaxial extensional, and simple shear flows, and find that both methods generate nearly identical results. The computational cost per time step for a free-draining BD simulation with the proposed bead-FF-spring model is about twice as high as the traditional bead-rod model with the midpoint algorithm of Liu [J. Chem. Phys. 90, 5826 (1989)]. Nevertheless, computations with the bead-FF-spring model are as efficient as those with the bead-rod model in extensional flow because the former allows larger time steps. Moreover, the Brownian contribution to the stress for the bead-FF-spring model is isotropic and therefore simplifies the calculation of the polymer stresses. In addition, hydrodynamic interaction can more easily be incorporated into the bead-FF-spring model than into the bead-rod model since the metric force arising from the non-Cartesian coordinates used in bead-rod simulations is absent from bead-spring simulations. Finally, with our newly developed bead-FF-spring model, existing computer codes for the bead-spring models can trivially be converted to ones for effective bead-rod simulations merely by replacing the usual FENE or Cohen spring law with a FENE-Fraenkel law, and this convertibility provides a very convenient way to perform multiscale BD simulations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87880/2/044911_1.pd

Publisher’s Note: “Brownian dynamics simulations with stiff finitely extensible nonlinear elastic-Fraenkel springs as approximations to rods in bead-rod models” [J. Chem. Phys. 124, 044911 (2006)]

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87879/2/179901_1.pd

MULTISPECIES REVENUE FUNCTION ESTIMATION FOR NORTH PACIFIC GROUNDFISH FISHERIES

Multiproduct, multispecies revenue functions are estimated for the midwater and bottom-trawl pollock fisheries off Alaska. There are strong year and seasonal effects on coefficient estimates, and the technology is joint in outputs for each major operation type. The model is a step toward prediction of fishery regulatory effects.Resource /Energy Economics and Policy,

Efficient estimation of binding free energies between peptides and an MHC class II molecule using coarse‐grained molecular dynamics simulations with a weighted histogram analysis method

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137767/1/jcc24845.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137767/2/jcc24845_am.pd