Gemini surfactants comprise two single-tailed surfactants connected by a linker at or near the hydrophilic headgroup. They display a variety of water-concentration-dependent lyotropic liquid crystal morphologies that are sensitive to surfactant molecular structure and the nature of the headgroups and counterions. Recently, an interesting dependence of the aqueous-phase behavior on the length of the linker has been discovered; odd-numbered linker length surfactants exhibit characteristically different phase diagrams than even-numbered linker surfactants. In this work, we investigate this “odd/even effect” using computer simulations, focusing on experimentally studied gemini dicarboxylates with Na+ counterions, seven nonterminal carbon atoms in the tails, and either three, four, five, or six carbon atoms in the linker (denoted Na-73, Na-74, Na-75, and Na-76, respectively). We find that the relative electrostatic repulsion between headgroups in the different morphologies is correlated with the qualitative features of the experimental phase diagrams, predicting destabilization of hexagonal phases as the cylinders pack close together at low water content. Significant differences in the relative headgroup orientations of Na-74 and Na-76 compared to those of Na-73 and Na-75 surfactants lead to differences in linker–linker packing and long-range headgroup–headgroup electrostatic repulsion, which affects the delicate electrostatic balance between the hexagonal and gyroid phases. Much of the fundamental insight presented in this work is enabled by the ability to computationally construct and analyze metastable phases that are not observable in experiments.

We develop ab initio force fields for alkylimidazolium-based ionic liquids (ILs) that predict the density, heats of vaporization, diffusion, and conductivity that are in semiquantitative agreement with experimental data. These predictions are useful in light of the scarcity of and sometimes inconsistency in experimental heats of vaporization and diffusion coefficients. We illuminate physical trends in the liquid cohesive energy with cation chain length and anion. These trends are different than those based on the experimental heats of vaporization. Molecular dynamics prediction of the room temperature dynamics of such ILs is more difficult than is generally realized in the literature due to large statistical uncertainties and sensitivity to subtle force field details. We believe that our developed force fields will be useful for correctly determining the physics responsible for the structure/property relationships in neat ILs.

The dynamics of water confined to nanometer-sized domains is important in a variety of applications ranging from proton exchange membranes to crowding effects in biophysics. In this work, we study the dynamics of water in gemini surfactant-based lyotropic liquid crystals (LLCs) using molecular dynamics simulations. These systems have well characterized morphologies, for example, hexagonal, gyroid, and lamellar, and the surfaces of the confining regions can be controlled by modifying the headgroup of the surfactants. This allows one to study the effect of topology, functionalization, and interfacial curvature on the dynamics of confined water. Through analysis of the translational diffusion and rotational relaxation, we conclude that the hydration level and resulting confinement length scale is the predominate determiner of the rates of water dynamics, and other effects, namely, surface functionality and curvature, are largely secondary. This novel analysis of the water dynamics in these LLC systems provides an important comparison for previous studies of water dynamics in lipid bilayers and reverse micelles.

The conformational properties of polymers in ionic liquids are of fundamental interest but not well understood. Atomistic and coarse-grained molecular models predict qualitatively different results for the scaling of chain size with molecular weight, and experiments on dilute solutions are not available. In this work, we develop a first-principles force field for poly(ethylene oxide) (PEO) in the ionic liquid 1-butyl 3-methylimidazolium tetrafluoroborate ([BMIM][BF4]) using symmetry adapted perturbation theory (SAPT). At temperatures above 400 K, simulations employing both the SAPT and OPLS-AA force fields predict that PEO displays ideal chain behavior, in contrast to previous simulations at lower temperature. We therefore argue that the system shows a transition from extended to more compact configurations as the temperature is increased from room temperature to the experimental lower critical solution temperature. Although polarization is shown to be important, its implicit inclusion in the OPLS-AA force is sufficient to describe the structure and energetics of the mixture. The simulations emphasize the difference between ionic liquids from typical solvents for polymers.

Molecular dynamics study of ionic liquids (ILs) is a challenging task. While accurate fully polarizable atomistic models exist, they are computationally too demanding for routine use. Most nonpolarizable atomistic models predict diffusion constants that are much lower than experiment. Scaled charge atomistic models are cost-effective and give good results for single component ILs but are in qualitative error for the phase behavior of mixtures, due to inaccurate prediction of the IL cohesive energy. In this work, we present an alternative approach for developing computationally efficient models that importantly preserves both the correct dynamics and cohesive energy of the IL. Employing a “top-down” approach, a hierarchy of coarse-grained models for BMIM+BF4– are developed by systematically varying the polarization/atomic resolution of the distinct functional groups. Parametrization is based on symmetry-adapted perturbation theory (SAPT) calculations involving the homomolecular species; all cross interactions are obtained from mixing rules, and there are no adjustable parameters. We find that enhanced dynamics from a united-atom description counteracts the effect of reduced polarization, enabling computationally efficient models that exhibit quantitative agreement with experiment for both static and dynamic properties. We give explicit suggestions for reduced-description models that are computationally more efficient, more accurate, and more fundamentally sound than existing nonpolarizable atomistic models.

Polymers exhibit interesting phase behavior in room temperature ionic liquids. For example poly(ethylene oxide) (PEO) displays a lower critical solution temperature (LCST) in [BMIM][BF4] with a critical temperature and concentration that are only weakly dependent on molecular weight, contrary to the behavior of polymers in other solvents. To shed light on the mechanism of the LCST, we study the phase behavior of PEO in [BMIM][BF4] using molecular dynamics (MD) simulations. The simulations show the signature of a phase transition as the temperature is increased. At low temperatures, interactions similar to a hydrogen bond are found between the imidazolium hydrogen and the PEO oxygen (HI–O H-bond) and the imidazolium hydrogen and the anion fluorines (HI–F H-bond). These interactions stabilize the mixed phase. A potential of mean force (PMF) analysis shows an entropic cost associated with the HI–O H-bond, which makes the bond formation unfavorable at higher temperatures, while the HI–F H-bond does not show a significant temperature dependence: This suggests that LCST phase separation is driven by the entropic penalty of the polymer for a PEO-cation hydrogen bond. We test the effect of scaling the charges on the [BMIM][BF4]. Interestingly, the scaled charge force-field does not predict a phase separation at any temperature, thus, emphasizing the pitfalls of charge scaling for mixtures.

We study the conformational properties of polymers in room temperature ionic liquids using theory and simulations of a coarse-grained model. Atomistic simulations have shown that single poly(ethylene oxide) (PEO) molecules in the ionic liquid 1-butyl 3-methyl imidazolium tetrafluoroborate ([BMIM][BF4]) are expanded at room temperature (i.e., the radius of gyration, Rg), scales with molecular weight, Mw, as Rg ∼ Mw0.9, instead of the expected self-avoiding walk behavior. The simulations were restricted to fairly short chains, however, which might not be in the true scaling regime. In this work, we investigate a coarse-grained model for the behavior of PEO in [BMIM][BF4]. We use existing force fields for PEO and [BMIM][BF4] and Lorentz–Berthelot mixing rules for the cross interactions. The coarse-grained model predicts that PEO collapses in the ionic liquid. We also present an integral equation theory for the structure of the ionic liquid and the conformation properties of the polymer. The theory is in excellent agreement with the simulation results. We conclude that the properties of polymers in ionic liquids are unusually sensitive to the details of the intermolecular interactions. The integral equation theory is sufficiently accurate to be a useful guide to computational work.

Polymer solutions present a significant computational challenge because chemical realism on small length scales can be important, but the polymer molecules are very large. In polyelectrolyte solutions, there is often the additional complexity that the molecules consist of hydrophobic and charged groups, which makes an accurate treatment of the solvent, water, crucial. One route to achieve this balance is through coarse-grained models where several atoms on a monomer are grouped into one interaction site. In this work, we develop a coarse grained (CG) model for sodium polystyrenesulfonate (NaPSS) in water using a methodology consistent with the MARTINI coarse-graining philosophy, where four heavy atoms are grouped into one CG site. We consider two models for water: polarizable MARTINI (POL) and big multipole water (BMW). In each case, interaction parameters for the polymer sites are obtained by matching the potential of mean force between two monomers to results of atomistic simulations. The force field based on the POL water provides a more reasonable description of polymer properties than that based on the BMW water. We study the properties of single chains using the POL force field. Fully sulfonated chains are rodlike (i.e., the root-mean-square radius of gyration, Rg, scales linearly with degree of polymerization, N). When the fraction of sulfonation, f, is 0.25 or less, the chain collapses into a cylindrical globule. For f = 0.5, pearl-necklace conformations are observed when every second monomer is sulfonated. The lifetime of a counterion around a polymer is on the order of 100 ps, suggesting that there is no counterion condensation. The model is computationally feasible and should allow one to study the effect of local chemistry on the properties of polymers in aqueous solution.

The behavior of polymers in ionic liquids is of technological and scientific interest. In this work we present atomistic simulations for the properties of isolated poly(ethylene oxide) (PEO) in the ionic liquid 1-butyl 3-methylimidazolium tetrafluoroborate ([BMIM][BF4]) and compare to the properties of the same polymer in water, at room temperature, for degrees of polymerization N ranging from 9 to 40. PEO chains are much more expanded in [BMIM][BF4] than in water. The root-mean-square radius of gyration, Rg, scales as Rg ∼ Nν with ν ≈ 0.9, and the distribution of end-to-end distance is bimodal, with coexisting extended and hairpin-like conformations. The simulations are consistent with polyelectrolyte behavior, i.e., Rg ∼ N, but the chains might be too short to be in the true scaling regime. (For comparison, Rg ∼ N0.5 in water.) [BMIM][BF4] is a much better solvent than water: In [BMIM][BF4] the solvation free energy of the monomer is 50% more negative, and the potential of mean force between two PEO 9-mers is significantly more repulsive than in water; the repulsion comes from energetic polymer–solvent interactions. The simulations suggest that the conformational behavior of PEO in ionic liquids is different from that in other common solvents, and computational studies of long chains will be interesting.

A new coarse-grained force field is developed for polyethylene glycol (PEG) in water. The force field is based on the MARTINI model but with the big multipole water (BMW) model for the solvent. The polymer force field is reparameterized using the MARTINI protocol. The new force field removes the ring-like conformations seen in simulations of short chains with the MARTINI force field; these conformations are not observed in atomistic simulations. We also investigate the effect of using parameters for the end-group that are different from those for the repeat units, with the MARTINI and BMW/MARTINI models. We find that the new BMW/MARTINI force field removes the ring-like conformations seen in the MARTINI models and has more accurate predictions for the density of neat PEG. However, solvent-separated-pairs between chain ends and slow dynamics of the PEG reflect its own artifacts. We also carry out fine-grained simulations of PEG with bundled water clusters and show that the water bundling can lead to ring-like conformations of the polymer molecules. The simulations emphasize the pitfalls of coarse-graining several molecules into one site and suggest that polymer–solvent systems might be a stringent test for coarse-grained force fields.

The dynamics of colloids and proteins in dense suspensions is of fundamental importance, from a standpoint of understanding the biophysics of proteins in the cytoplasm and for the many interesting physical phenomena in colloidal dispersions. Recent experiments and simulations have raised questions about our understanding of the dynamics of these systems. Experiments on vesicles in nematic fluids and colloids in an actin network have shown that the dynamics of particles can be “non-Gaussian”; that is, the self-part of the van Hove correlation function, Gs(r,t), is an exponential rather than Gaussian function of r, in regimes where the mean-square displacement is linear in t. It is usually assumed that a linear mean-square displacement implies a Gaussian Gs(r,t). In a different result, simulations of a mixture of proteins, aimed at mimicking the cytoplasm of Escherichia coli, have shown that hydrodynamic interactions (HI) play a key role in slowing down the dynamics of proteins in concentrated (relative to dilute) solutions. In this work, we study a simple system, a dilute tracer colloidal particle immersed in a concentrated solution of larger spheres, using simulations with and without HI. The simulations reproduce the non-Gaussian Brownian diffusion of the tracer, implying that this behavior is a general feature of colloidal dynamics and is a consequence of local heterogeneities on intermediate time scales. Although HI results in a lower diffusion constant, Gs(r,t) is very similar to and without HI, provided they are compared at the same value of the mean-square displacement.

Molecular simulations play an important role in establishing structure–property relations in complex fluids such as room-temperature ionic liquids. Classical force fields are the starting point when large systems or long times are of interest. These force fields must be not only accurate but also transferable. In this work, we report a physically motivated force field for the ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]) based on symmetry-adapted perturbation theory. The predictions (from molecular dynamics simulations) of the liquid density, enthalpy of vaporization, diffusion coefficients, viscosity, and conductivity are in excellent agreement with experiment, with no adjustable parameters. The explicit energy decomposition inherent in the force field enables a quantitative analysis of the important physical interactions in these systems. We find that polarization is crucial and there is little evidence of charge transfer. We also argue that the often used procedure of scaling down charges in molecular simulations of ionic liquids is unphysical for [BMIM][BF4]. Because all intermolecular interactions in the force field are parametrized from first-principles, we anticipate good transferability to other ionic liquid systems and physical conditions.Keywords: force field; ionic liquids; polarizable; SAPT;

The self-assembly behavior of gemini (dimeric or twin-tail) dicarboxylate disodium surfactants is studied using molecular dynamics simulations. A united atom model is employed for the surfactants with fully atomistic counterions and water. This gemini architecture, in which two single tailed surfactants are joined through a flexible hydrophobic linker, has been shown to exhibit concentration-dependent aqueous self-assembly into lyotropic phases including hexagonal, gyroid, and lamellar morphologies. Our simulations reproduce the experimentally observed phases at similar amphiphile concentrations in water, including the unusual ability of these surfactants to form gyroid phases over unprecedentedly large amphiphile concentration windows. We demonstrate quantitative agreement between the predicted and experimentally observed domain spacings of these nanostructured materials. Through careful conformation analyses of the surfactant molecules, we show that the gyroid phase is electrostatically stabilized related to the lamellar phase. By starting with a lamellar phase, we show that use of a bulkier N(CH3)4+ counterion in place of Na+ drives the formation of a gyroid phase. Decreasing the charge on the surfactant headgroups by carboxylate protonation decreases the degree of order in the lamellar phase. Using our models, we show that the translational diffusion of water and the Na+ counterions is decreased by several orders of magnitude over the studied concentration range, and we attribute these effects to strong correlations between the mobile species and the surfactant headgroups.

An important puzzle in membrane biophysics is the difference in the behaviors of lysine (Lys) and arginine (Arg) based peptides at the membrane. For example, the translocation of poly-Arg is orders of magnitude faster than that of poly-Lys. Recent experimental work suggests that much of the difference can be inferred from the phase behavior of peptide/lipid mixtures. At similar concentrations, mixtures of phosphatidylethanolamine (PE) and phosphatidylserine (PS) lipids display different phases in the presence of these polypeptides, with a bicontinuous phase observed with poly-Arg peptides and an inverted hexagonal phase observed with poly-Lys peptides. Here we show that simulations with the coarse-grained (CG) BMW-MARTINI model reproduce the experimental results. An analysis using atomistic and CG models reveals that electrostatic and glycerol–peptide interactions play a crucial role in determining the phase behavior of peptide–lipid mixtures, with the difference between Arg and Lys arising from the stronger interactions of the former with lipid glycerols. In other words, the multivalent nature of the guanidinium group allows Arg to simultaneously interact with both phosphate and glycerol groups, while Lys engages solely with phosphate; this feature of amino acid/lipid interactions has not been emphasized in previous studies. The Arg peptides colocalize with PS in regions of high negative Gaussian curvature and stabilize the bicontinuous phase. Decreasing the strength of either the electrostatic interactions or the peptide–glycerol interactions causes the inverted hexagonal phase to become more stable. The results highlight the utility of CG models for the investigation of phase behavior but also emphasize the subtlety of the phenomena, with small changes in specific interactions leading to qualitatively different phases.

The properties of short chains of poly-(styrene)-co-(styrene sulfonate) are studied using atomistic molecular dynamics simulations with explicit solvent. We study single 8-mers and 16-mers with two species of counterions, Na+ and Mg2+, and for various degrees of sulfonation, f. We find that single trajectories do not efficiently sample configurational space, even for fairly long 100-ns simulations, because of rotational barriers caused by nonbonded interactions. Hamiltonian replica exchange molecular dynamics (HREMD) simulations or averages over multiple trajectories are required in order to obtain equilibrium properties. A polystyrene sulfonate chain adopts collapsed conformations at low f, in which the sulfonate groups are located outside the globule and benzene rings form the inner region, and adopts extended conformations as f is increased. Interestingly, the pair correlation functions between side groups of polystyrene chains are not sensitive to f and species of counterion, i.e., the balance of electrostatic repulsion between charged groups and hydrophobic attraction between benzene rings is achieved by conformational change in a way preserving pair correlations between side groups in a polymer chain. For Na+ counterions, no localization is observed in the simulations. For Mg2+ counterions, there is a large free energy barrier to contact pair formation between the sulfonate groups and the Mg2+ counterions. As a consequence we do not observe the formation or breaking of contact pairs during the course of a simulation. The simulations provide insight into the important interactions and correlations in polyelectrolyte solutions.

The control of catalytic activity using molecular self-assembly is of fundamental interest. Recent experiments (Muller et al., Angew. Chem., Int. Ed., 2009, 48, 922–925) have demonstrated that two sequence isomers of β-peptides show remarkably different activity as an amine catalyst for a retro-aldol cleavage reaction, a difference attributed to the ability of one of the sequences to form large aggregates. The self-assembly and catalytic activity of these two isomers are investigated using constant pH molecular dynamics (CPHMD), for an atomistic model of β-peptides in implicit solvent. Simulations show that the globally amphiphilic (GA) isomer, which experimentally has high activity, forms large aggregates, while the non-GA isomer forms aggregates that are at most three or four molecules in size. The pKa shift of the βK-residues is significantly higher in the GA isomers that make a large aggregate. Since the decrease in pKa of the side-chain ammonium group is the main driving force for amine catalysis, the calculations are consistent with experiment. We find that the buried βK residues become entirely deprotonated, and the pKa shift for other titratable βK residues is accompanied mainly by a clustering of solvent exposed βK residues. We conclude that simulations can be used to understand catalytic activity due to self-assembly.

The effect of salt on the dynamics of water molecules follows the Hofmeister series. For some “structure-making” salts, the self-diffusion coefficient of the water molecules, D, decreases with increasing salt concentration. For other “structure-breaking” salts, D increases with increasing salt concentration. In this work, the concentration and temperature dependence of the self-diffusion of water in electrolyte solutions is studied using molecular dynamics simulations and pulsed-field-gradient NMR experiments; temperature-dependent viscosities are also independently measured. Simulations of rigid, nonpolarizable models at room temperature show that none of the many models tested can reproduce the experimentally observed trend for the concentration dependence of D; that is, the models predict that D decreases with increasing salt concentration for both structure-breaking and structure-making salts. Predictions of polarizable models are not in agreement with experiment either. These results suggest that many popular water models do not accurately describe the dynamic nature of the hydrogen bond network of water at room temperature. The simulations are in qualitative agreement, however, with experimental results for the temperature dependence of water dynamics; simulations and experiment show an Arrhenius dependence of D with temperature, T, with added salt, that is, ln D ∼ 1/T, over a range of temperatures above the freezing point of water.

We present a new coarse-grained (CG) model for simulations of lipids and peptides. The model follows the same topology and parametrization strategy as the MARTINI force field but is based on our recently developed big multipole water (BMW) model for water (J. Phys. Chem. B2010, 114, 10524–10529). The new BMW-MARTINI force field reproduces many fundamental membrane properties and also yields improved energetics (when compared to the original MARTINI force-field) for the interactions between charged amino acids with lipid membranes, especially at the membrane–water interface. A stable attachment of cationic peptides (e.g., Arg8) to the membrane surface is predicted, consistent with experiment and in contrast to the MARTINI model. The model predicts electroporation when there is a charge imbalance across the lipid bilayer, an improvement over the original MARTINI. Moreover, the pore formed during electroporation is toroidal in nature, similar to the prediction of atomistic simulations but distinct from results of polarizable MARTINI for small charge imbalances. The simulations emphasize the importance of a reasonable description of the electrostatic properties of water in CG simulations. The BMW-MARTINI model is particularly suitable for describing interactions between highly charged peptides with lipid membranes, which is crucial to the study of antimicrobial peptides, cell penetrating peptides, and other proteins/peptides involved in the remodeling of biomembranes.

The classical view of the hydrophobic effect is that the association of hydrophobic molecules is entropy-driven and caused by the increase in the entropy of water. In this work, we investigate the thermodynamics of association of amphiphilic molecules that consist of a hydrophobic block and a hydrophilic block. Using atomistic simulations, we calculate the potential of mean force between molecules and obtain the entropic and energetic contributions from calculations at two temperatures. For purely hydrophobic molecules, the association is entropy driven, but for the block copolymers the thermodynamic driving force is sensitive to the conditions: The association between block copolymers is energy-driven in pure water and methanol but is entropy-driven in aqueous solutions with high concentrations of added salt. These results demonstrate that the driving force for association in amphiphilic molecules is sensitive to conditions, and the classical view of the hydrophobic effect is not universal.Keywords: amphiphilic molecules; association; energy; entropy; free energy; hydrophobic effect; PMF; thermodynamic driving force;

The hydrophobic effect plays a central role in many biological processes, including protein folding and aggregation. The hydrophobic interaction between solutes, such as helical peptides, is believed to be of entropic origin and driven by the increase in the entropy of water due to association. In this work, we examine the association between peptides in water using several coarse-grained (CG) models, such as MARTINI (MAR), polarizable MARTINI (POL), and big multipole water (BMW) models, where four atomistic water molecules are grouped into a single CG unit. All models predict that a pair of helical peptides (Ala20 and Leu20) has favorable association free energy. The BMW model is the only model, however, in which this association is entropy-driven, as has been previously established with atomistic simulations and experiments. The MAR and POL models, where the CG water particles do not have a quadrupole moment, predict an enthalpy-driven association, with a negligible entropy change upon association. Similarly, the association of two rigid cylinders in water is found to be enthalpy-driven when the water is described with the CG model of Shinoda et al. that includes a soft-core nonelectrostatic interaction, while BMW predicts an entropy-driven association. These results emphasize the importance of electrostatic interactions in water for the qualitative features of the thermodynamics of biophysical systems.Keywords: coarse-grained models; entropy-driven hydrophobic association; entropy−enthalpy compensation; water quadrupole interactions;

A new coarse-grained (CG) model is developed for water. Each CG unit consists of three charged sites, and there is an additional nonelectrostatic soft interaction between central sites on different units. The interactions are chosen to mimic the properties of 4-water clusters in atomistic simulations: the nonelectrostatic component is modeled using a modified Born−Mayer−Huggins potential, and the charges are chosen to reproduce the dipole moment and quadrupole moment tensor of 4-water clusters from atomistic simulations. The parameters are optimized to reproduce experimental data for the compressibility, density, and permittivity of bulk water and the surface tension and interface potential for the air−water interface. This big multipole water (BMW) model represents a qualitative improvement over existing CG water models; for example, it reproduces the dipole potential in membrane−water interface when compared to experiment, with modest additional computational cost as compared to the popular MARTINI CG model.

Recent experimental studies have revealed interesting sequence dependence in the antimicrobial activity of β-peptides, which suggests the possibility of a rational design of new antimicrobial agents. To obtain insight into the mechanism of membrane activity, we present a computer simulation study of the adsorption of these molecules to a single-component lipid membrane. Two classes of molecules are investigated: 10-residue oligomers of 14-helical sequences, and four sequences of random copolymeric β-peptides. The oligomers of interest are globally amphiphilic (GA) and nonglobally amphiphilic (non-GA) sequences of 10-residue, 14-helical sequences. In solution and at the interface, all oligomers maintain a helical structure throughout the simulation. The penetration of the molecules into the membrane and the orientation of the molecules at the interface depend strongly on the sequence. We attribute this to the propensity of the β-phenylalanine (βF) residues for membrane penetration. For the four sequences of random copolymeric β-peptides, simulations of an implicit solvent and membrane model show that the strength of adsorption of the polymers is strongly correlated with their efficiency to segregate the hydrophobic and cationic residues. The simulations suggest simple strategies for the design of candidates for antimicrobial β-peptides. Collectively, these results further support the conclusion from several recent studies that neither global amphiphilicity nor regular secondary structure is required for short peptides to effectively interact with the membrane. Moreover, although we study only the binding process, the fact that there is a correlation between the sequence dependence in the calculated binding properties and the experimentally observed antimicrobial activity suggests that efficient binding to the membrane might be a good predictor for high antimicrobial activity.

Oligomers of β-peptides with cyclic residues make very stable helices where the amphiphilicity can be tailored via the sequence. These molecules display large-scale hierarchical self-assembly that is very sensitive to the sequence. For example, the globally amphiphilic (GA) sequence of one molecule, βY−(ACHC−ACHC−βK)3 (model A), self-assembles into long cylinders, which can display a nematic phase, but the nonglobally amphiphilic (non-GA) sequence does not. Interestingly, for a closely related sequence, βY−(ACHC−βF−βK)3 (model B), the opposite is true; that is, the non-GA sequence self-assembles into long hollow cylinders, and the GA sequence does not. In this work, the pair and many-body potential of mean force (PMF) between β-peptides is studied using computer simulations with explicit and implicit solvent. The PMF studies rationalize the experimentally observed trends. In particular, for the sequences that form hollow cylinders, the most stable configuration of a pair of molecules is when they are side-to-side and parallel. The two sequences that do make cylinders have side-to-side parallel configurations with a slight curvature at the minimum in the triplet PMF. The implicit solvent simulations are in qualitative accord with explicit solvent simulations for the pair PMF, suggesting that one could use multibody PMF studies with implicit solvent models to provide insight into the self-assembly of complex molecules.

The effect of peptides on the growth of ice crystals are studied using molecular dynamics simulations. The growth of the ice crystal is simulated at a supercooling of 14 K, and the effect of a single tetrapeptide on the growth rate is calculated. For pure ice the simulated crystal grows at a rate comparable to experiment. When a peptide molecule is added near the interface, the growth rate is diminished significantly, by up to a factor of 5 for Gly-Pro-Ala-Gly and a factor of 3 for Gly-Gly-Ala-Gly. The retardation occurs via the binding of the peptide to the ice surface, suppression of ice growth near the binding site, and eventual growth of the crystal around the bound peptide. The peptide with a proline residue is more effective in retarding the crystal growth, and this can be understood from the conformation of the peptide within the frozen ice phase after overgrowth. The simulations suggest that short peptides can be effective antifreeze agents.

The sequence-directed organization of self-assembled monolayers of amphiphilic β-peptides adsorbed on gold surfaces is studied using Monte Carlo simulations. A phenomenological model is presented in which each (helical) molecule is represented by a rigid nanorod; side groups are placed at appropriate locations. This model can distinguish between globally amphiphilic (GA) and nonglobally amphiphilic (iso-GA) sequence isomers. The simulations show that the GA isomers have a high degree of orientational order that is not exhibited by the iso-GA isomers, which is consistent with experiment (Pomerantz et al. Chem. Mater. 2007, 19, 4436). The effect of surface coverage and relative strength of electrostatic, hydrophilic, and hydrophobic interactions on the self-assembly of β-peptides is quantified.

In Escherichia coli, ribosomes concentrate near the cylindrical wall and at the endcaps, whereas the chromosomal DNA segregates in the more centrally located nucleoid. A simple statistical model recovers the observed ribosome-nucleoid segregation remarkably well. Plectonemic DNA is represented as a hyperbranched hard-sphere polymer, and multiple ribosomes that simultaneously translate the same mRNA strand (polysomes) are represented as freely jointed chains of hard spheres. There are no attractive interactions between particles, only excluded-volume effects. At realistic DNA and ribosome concentrations, segregation arises primarily from two effects: the DNA polymer avoids walls to maximize conformational entropy, and the polysomes occupy the empty space near the walls to maximize translational entropy. In this complex system, maximizing total entropy results in spatial organization of the components. Due to coupling of mRNA to DNA through RNA polymerase, the same entropic effects should favor the placement of highly expressed genes at the interface between the nucleoid and the ribosome-rich periphery. Such a placement would enable efficient cotranscriptional translation and facile transertion of membrane proteins into the cytoplasmic membrane. Finally, in the model, monofunctional DNA polymer beads representing the tips of plectonemes preferentially locate near the cylindrical wall. This suggests that initiation of transcription may occur preferentially near the ribosome-rich periphery.

The effect of macromolecular crowding on the rates of association reactions are investigated using theory and computer simulations. Reactants and crowding agents are both hard spheres, and when two reactants collide they form product with a reaction probability, prxn. A value of prxn < 1 crudely mimics the fact that proteins must be oriented properly for an association reaction to occur. The simulations show that the dependence of the reaction rate on the volume fraction of crowding agents varies with the reaction probability. For reaction probabilities close to unity where most of encounters between reactants lead to a reaction, the reaction rate always decreases as the volume fraction of crowding agents is increased due to the reduced diffusion coefficient of reactants. On the other hand, for very small reaction probabilities where, in most of encounters, the reaction does not occur, the reaction rate increases with the volume fraction of crowding agents—in this case, due to the increase probability of a recollision. The Smoluchowski theory refined with the radiation boundary condition and the radial distribution function at contact is in quantitative agreement with simulations for the reaction rate constant and allows the quantitative analysis of both effects separately.

The effect of macromolecular crowding on the binding of ligands to a receptor near membranes is studied using Brownian dynamics simulations. The receptor is modeled as a reactive patch on a hard surface and the ligands and crowding agents are modeled as spheres that interact via a steep repulsive interaction potential. When a ligand collides with the patch, it reacts with probability prxn. The association rate constant (k∞) can be decomposed into contributions from diffusion-limited (kD) and reaction-limited (kR) rates, i.e., 1/k∞ = 1/kD + 1/kR. The simulations show that kD is a nonmonotonic function of the volume fraction of crowding agents for receptors of small sizes. kR is always an increasing function of the volume fraction of crowding agents, and the association rate constant k∞ determined from both contributions has a qualitatively different dependence on the macromolecular crowding for high and low values of the reaction probability prxn. The simulation results are used to predict the velocity of the membrane protrusion driven by actin filament elongation. Based on the simple model where the protrusive force on the membrane is generated by the intercalation of actin monomers between the membrane and actin filament ends, we predict that crowding increases the local concentration of actin monomers near the filament ends and hence accelerates the membrane protrusion.