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.

We apply the recently developed replica exchange with solute tempering (REST) to three large solvated peptide systems: an α-helix, a β-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.The replica exchange method (REM) has become very popular in the sampling of biomolecular systems. [1][2][3][4][5][6] However, the REM is restricted to relatively small systems, since the required number of replicas scales as O(f 1/2 ), where f is the number of degrees of freedom in the system. 7 To overcome this problem, we recently introduced replica exchange with solute tempering (REST) 8 for all-atom simulations in explicit water. In our original study, we tested REST on an alanine dipeptide dissolved in explicit water, a system with about 1500 atoms, and suggested that the required number of replicas now scales as O(f p 1/2 ), where f p is the number of degrees of freedom in the central group. In addition, we suggested that the speedup versus the REM, in terms of converging to the correct underlying distribution, is . In the current study, we broaden the application of REST to three large solvated peptide systems (α-helix, β-hairpin, and TrpCage) to offer an assessment of the efficiency of REST.Imposing detailed balance on the standard temperature replica exchange (REM) 1,2 operation results in the acceptance criterion , and E(X n ) is the potential energy of the system for the nth replica with configuration X n . For a protein system, the energy is composed of three terms:where E pp , E pw , and E ww are, respectively, the internal energy of the protein, the interaction energy between the protein and water, and the self-interaction energy of the water molecules. Properly solvating a protein system typically requires several thousand water molecules; hence, the self-interaction between the water molecules usually vastly dominates the other terms, that is, |E pp |, |E pw | ≪ |E ww |.The main disadvantage of the REM is that the system size causes the required number of replicas to increase rapidly, 7 roughly as O(f 1/2 ), where f is the number of degrees of freedom in the system. However, the presence of the water self-interaction energy, E ww , has two previously underappreciated benefits: (i) Changes in E pw are partially compensated by opposite changes in E ww , since both the magnitude of E pw and the number of water molecul...

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. 1 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.

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.