Interlamellar coupling of phospholipid bilayers in liposomes: an emergent property of lipid rearrangement.

The thermal phase behaviors of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) large unilamellar vesicles (LUVs) and multilamellar vesicles (MLVs) were compared by fluorescence spectroscopy, using PPDPC (1-palmitoyl-2[10-(pyren-1-yl)]decanoyl-sn-glycero-3-phosphocholine) as a reporter, in parallel with differential scanning calorimetry (DSC). A striking difference is seen between MLVs and LUVs in the lateral organizational dynamics of PPDPC, in particular, below the main phase transition temperature T(m), with efficient clustering of PPDPC into fluid microdomains in the L(beta') and P(beta') (ripple) phases of DPPC MLVs. In the P(beta') phase of MLVs, the probe is likely to become enriched in linear line defects, restricting intermolecular collisions to occur in a quasi one-dimensional system. In contrast, fluorescence and DSC data both suggest that the P(beta') phase is not well-defined in LUVs. Fluorescence anisotropy for 1-palmitoyl-2-[3-(diphenylhexatrienyl)propanoyl]-sn-glycero-3-phosphocholine (DPH-PC) revealed similar acyl chain order for both LUVs and MLVs in the L(beta') and P(beta') phases. However, for MLVs with this probe, T(m) determined from anisotropy was elevated by 0.7 degrees, with higher anisotropy evident in the L(alpha) phase compared to LUVs. These differences in the thermal phase behavior of the two types of liposomes are likely to derive from the augmented acyl chain order due to cooperative coupling of the lamellae of DPPC MLVs, thus manifesting in new, emerging material properties in the latter type of bilayer membrane assembly, as reflected in the organizational dynamics of the pyrene-labeled analogue.

Replica exchange with solute tempering: efficiency in large scale systems.

We apply the recently developed replica exchange with solute tempering (REST) to three large solvated peptide systems: an alpha-helix, a beta-hairpin, and a TrpCage, with these peptides defined as the "central group". We find that our original implementation of REST is not always more efficient than the replica exchange method (REM). Specifically, we find that exchanges between folded (F) and unfolded (U) conformations with vastly different structural energies are greatly reduced by the nonappearance of the water self-interaction energy in the replica exchange acceptance probabilities. REST, however, is expected to remain useful for a large class of systems for which the energy gap between the two states is not large, such as weakly bound protein-ligand complexes. Alternatively, a shell of water molecules can be incorporated into the central group, as discussed in the original paper.

Effect of ions on the hydrophobic interaction between two plates.

We use molecular dynamics simulations to investigate the solvent mediated attraction and drying between two nanoscale hydrophobic surfaces in aqueous salt solutions. We study these effects as a function of the ionic charge density, that is, the ionic charge per unit ionic volume, while keeping the ionic diameter fixed. The attraction is expressed by a negative change in the free energy as the plates are brought together, with enthalpy and entropy changes that both promote aggregation. We find a strong correlation between the strength of the hydrophobic interaction and the degree of preferential binding/exclusion of the ions relative to the surfaces. The results show that amplification of the hydrophobic interaction, a phenomenon analogous to salting-out, is a purely entropic effect and is induced by high-charge-density ions that exhibit preferential exclusion. In contrast, a reduction of the hydrophobic interaction, analogous to salting-in, is induced by low-charge-density ions that exhibit preferential binding, the effect being either entropic or enthalpic. Our findings are relevant to phenomena long studied in solution chemistry, as we demonstrate the significant, yet subtle, effects of electrolytes on hydrophobic aggregation and collapse.

Serial replica exchange.

Parallel tempering (or the replica exchange method (REM)) is a powerful method for speeding up the sampling of conformational states of systems with rough energy landscapes, like proteins, where stable conformational states can be separated by large energy barriers. The usual implementation of the REM is performed on local computer clusters (or parallel processors) where the different replicas must be run synchronously. Here, we present serial replica exchange (SREM), a method that is equivalent to the standard REM in terms of efficiency yet runs asynchronously on a distributed network of computers. A second advantage is the method's greatly enhanced fault tolerance, which enables the study of biological systems on worldwide distributed computing environments, such as Folding@Home. For proof of concept, we apply the SREM to a single alanine dipeptide molecule in explicit water. We show that the SREM reproduces the thermodynamic and structural properties determined by the REM.