J.J. López Cascales

HYDRO: a computer program for the prediction of hydrodynamic properties of macromolecules

HYDRO is a program for the calculation of sedimentation and diffusion coefficients, rotational relaxation times, and intrinsic viscosities of rigid macromolecules of arbitrary shape that are represented by bead models. Actually, HYDRO contains various FORTRAN callable subroutines that can be linked to the users own programs to account for variability of shape or flexibility. Some hints are given for the use of HYDRO in various situations.

Molecular dynamics simulation of a charged biological membrane

A molecular dynamics simulation of a membrane with net charge in its liquid‐crystalline state was carried out. It was modeled by dipalmitoylphosphatidylserine lipids with net charge, sodium ions as counterions and water molecules. The behavior of this membrane differs from that was shown by other membranes without a net charge as a consequence of strong Coulomb interaction between atoms of adjacent phospholipids. The most remarkable effect produced by such interaction between neighboring lipids is a reduction of the surface area per phospholipid compared to an uncharged membrane. In addition, other properties of the membrane were also affected by this interaction between adjacent lipids such as the atom distribution across the membrane, the diffusion coefficient of the different components of the membrane and the order parameter of the phospholipid hydrocarbon region. Some comparisons of this membrane with dipalmitoylphosphatidylcholine membrane without net charge at similar conditions are presented.

Study of the Benzocaine Transfer from Aqueous Solution to the Interior of a Biological Membrane

The precise molecular mechanism of general anesthetics remains unknown. It is therefore important to understand where molecules with anesthetic properties localize within biological membranes. We have determined the free energy profile of a benzocaine molecule (BZC) across a biological membrane using molecular dynamics simulation. We use an asymmetric phospholipid bilayer with DPPS in one leaflet of a DPPC bilayer (Lopez Cascales et al. J. Phys. Chem. B 2006, 110, 2358-2363) to model a biological bilayer. From the free energy profile, we predict the zone of actuation of a benzocaine is located in the hydrocarbon region or at the end of the lipid head, depending of the presence of charged lipids (DPPS) in the leaflet. We observe a moderate increase in the disorder of the membrane and in particular an increase in the disorder of DPPS. Static and dynamic physicochemical properties of the benzocaine, such as its dipole orientation, translational diffusion coefficient, and rotational relaxation time were measured.

Study of the effect of Na+ and Ca2+ ion concentration on the structure of an asymmetric DPPC/DPPC + DPPS lipid bilayer by molecular dynamics simulation.

A molecular dynamics simulation study of the steady and dynamic properties of an asymmetric phospholipid bilayer was carried out in the presence of sodium or calcium ions. The asymmetric lipid bilayer was seen to resemble a cellular membrane of an eukaryotic cell, which was modeled by dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylserine (DPPS), placing the DPPS in one of the two leaflets of the lipid bilayer. From a numerical analysis of the simulated trajectories, information was obtained with atomic resolution for both membrane leaflet concerning the effect of bilayer asymmetry on different properties of the lipid/water interface, such as the translational diffusion coefficient and rotational relaxation time of the water molecules, lipid hydration, and residence time of water around different lipid atoms. In addition, information related to lipid conformation, and lipid-lipid interactions was also analyzed.

EFFECT OF LITHIUM AND SODIUM IONS ON A CHARGED MEMBRANE OF DIPALMITOYLPHOSPHATIDYLSERINE : A STUDY BY MOLECULAR DYNAMICS SIMULATION

Abstract We describe a series of molecular dynamics simulations performed on a model of charged lipid bilayer (dipalmitoyl-phosphatidylserine) and water, in presence of sodium and lithium ions, with an atomic detail. The structure of the lipid membranes was strongly affected by the presence of lithium, as manifested by the observation of a transition from a disordered to a gel state. Concerning the mechanism of such a transition, it was associated to the dehydration that we detected in the lipid-water interface in the presence of lithium. This dehydration introduced an increase in the lipid-lipid interactions, and as a consequence, a diminution of the disorder of the membrane. When both types of ions are present in the aqueous phase, lithium shown a special affinity for the lipid membrane displacing almost all the sodium ions toward the middle of the water layer. As a result, we observed remarkable differences in the atom and electric field distributions across the lipid membrane. Concerning the diffusion and orientation of water molecules across the lipid-water interface, we also observed a strong dependency of the type ion. On the other hand, the mobility and the hydration shell of lithium and sodium ions are strongly perturbed by the presence of the charged lipid bilayer. The lipid layer was responsible for a dehydration of the ions compared to bulk water. This dehydration was compensated by an increase of coordination number of the ions with the lipid oxygens. Also, the residence times of water in the first hydration shell of lithium and sodium ions are perturbed by the presence of the lipid membrane.

Simulation of polymer chains in elongational flow. Steady‐state properties and chain fracture

The behavior of polymer chains in steady, uniaxial elongational flows is studied using the Brownian dynamics simulation technique. Two different types of chain models are considered. One is the bead‐and‐spring Rouse chain and the other is a chain with breakable connectors that obey a Morse potential. The dynamics of Rouse chains and Morse chains is simulated both without and with hydrodynamic interaction (HI) between chain elements. From the simulated trajectories, steady‐state properties such as chain dimensions and elongational viscosities are calculated. When HI is accounted for by using the Rotne–Prager–Yamakawa tensor, the calculated dimensions and viscosities are appreciably lower than when it is neglected. Carrying out simulations with varying elongational rate, it is possible to observe stretching and finally the fracture of the polymer chains. The critical elongational rate, corresponding to infinite elongation in the case of Rouse chains, and the fracture of the Morse chains has been characteriz...

Thermodynamic study of benzocaine insertion into different lipid bilayers

Despite the general consensus concerning the role played by sodium channels in the molecular mechanism of local anesthetics, the potency of anaesthetic drugs also seems to be related with their solubility in lipid bilayers. In this respect, this work represents a thermodynamic study of benzocaine insertion into lipid bilayers of different compositions by means of molecular dynamics simulation. Thus, the free energy profiles associated with benzocaine insertion into symmetric lipid bilayers composed of different proportions of dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylserine were studied. From the simulation results, a maximum in the free energy (ΔG) profile was measured in the region of the lipid/solution interface. This free energy barrier appears to be very much dependent on the lipid composition of the membrane. On the other hand, the minimum free energy (ΔG) within the bilayer remained almost independent of the lipid composition of the bilayer. By repeating the study at different temperatures, it was seen how the spontaneity of benzocaine insertion into the lipid bilayer is due to an increase in the entropy associated with the process.

MOLECULAR DYNAMICS SIMULATION OF A DYE MOLECULE IN THE INTERIOR OF A BILAYER : 1,6-DIPHENYL-1,3,5-HEXATRIENE IN DIPALMITOYLPHOSPHATIDYLCHOLINE

A molecular dynamics simulation was carried out for a dipalmitoylphosphatidylcholine (DPPC) membrane in its liquid crystalline state containing different concentrations of the dye molecule 1,6-diphenyl-1,3,5-hexatriene (DPH). From a numerical analysis of the trajectories, we obtained information concerning structural changes of the membrane due to the presence of the probe and some hydrodynamic information concerning the probe itself. The hydrodynamic properties regarding dye molecules that have been reported in this article are: rotational and translational diffusion coefficient and relaxation times. From this analysis, we estimated a range of values of 0.6-0.9 cP for the micro-viscosity in the mid-membrane. These simulations also afforded us some information regarding structural changes in the membrane as a consequence of the presence of the fluorescent dyes at different concentrations. Thus, the disorder inside the membrane, the surface area per lipid and thickness of the membrane were also investigated.

A DMPA Langmuir monolayer study: from gas to solid phase. An atomistic description by molecular dynamics Simulation.

In this work, a DMPA Langmuir monolayer at the air/water interface was studied by molecular dynamics simulations. Thus, an atomistic picture of a Langmuir monolayer was drawn from its expanded gas phase to its final solid condensed one. In this sense, some properties of monolayers that were traditionally poorly or even not reproduced in computer simulations, such as lipid domain formation or pressure-area per lipid isotherm, were properly reproduced in this work. Thus, the physical laws that control the lipid domain formation in the gas phase and the structure of lipid monolayers from the gas to solid condensed phase were studied. Thanks to the atomistic information provided by the molecular dynamics simulations, we were able to add valuable information to the experimental description of these processes and to access experimental data related to the lipid monolayers in their expanded phase, which is difficult or inaccessible to study by experimental techniques. In this sense, properties such as lipids head hydration and lipid structure were studied.

Simulation of non-linear models for polymer chains in flowing solutions

Two non-linear bead and spring models are considered for the Brownian dynamics simulation of the behaviour of polymer chains in a dilute solution under shear or elongational flow. One of them is the HYBRID model whose springs are Hookean at low elongation, and beyond some spring length they follow a Morse potential with a given dissociation energy. This model is suitable for studying polymer fracture in strong flows. In this paper we describe the model and check that it has the proper behaviour in the two regions. The second model is a chain of finitely extensible, non-linear elastic (FENE) springs. Our simulations show several features of the FENE model that agree well with observation. In shear flow, the deformation of the FENE chain at high shear rate deviates from the square law followed at low shear, in agreement with some experiments. The model also predicts the typical shear-thinning, non-Newtonian behaviour of the shear viscosity. In elongational flows, the variation of the chain properties with the elongation rate shows a rather sharp increase at some critical rate that is reminiscent of the so-called coil-stretch transition.