Markov State Models provide a framework for understanding the fundamental states and rates in conformational dynamics of biomolecules. We describe an improved protocol constructing from molecular simulations. The new includes advances clustering, data preparation, model estimation; these improvements lead to significant increases accuracy, as assessed by ability recapitulate equilibrium kinetic properties reference systems. A high-performance implementation this protocol, provided...

The tendency of amphiphilic molecules to form micelles in aqueous solution is a consequence the hydrophobic effect. fundamental difference between micelle assembly and macroscopic phase separation stoichiometric constraint that frustrates demixing polar groups. We present theory for combines account this with description driving force. latter arises from length scale dependence solvation. theoretical predictions temperature surfactant chain critical concentrations nonionic surfactants agree...

We present a lattice model of water confined in hydrophobic nanotube. Using analytical methods and computer simulation, we find conditions where filled empty tubes can be degenerate equilibrium. further that flow molecules through tube with appropriate but simple stochastic rules interpreted as conduction pulse-like fashion. These two results are consistent an atomistic molecular dynamics study this system [Hummer et al. Nature 2001, 414, 188−190]. Finally, analyze transitions between the...

Dynamical four-point susceptibilities measure the extent of spatial correlations in dynamics glass forming systems. We show how these depend on lengthscales that necessarily form part their definition. The behavior is estimated by means an analysis terms renewal processes within context dynamic facilitation. analytic results are confirmed numerical simulations atomistic model former, and two kinetically constrained models. Hence we argue scenario predicted facilitation approach generic.

With molecular dynamics simulations of a fluid mixture classical particles interacting with pairwise additive Weeks-Chandler-Andersen potentials, we consider the time series particle displacements and thereby determine distributions for local persistence times exchange times. These basic characterizations glassy are studied over range supercooled conditions were shown to have behaviors, most notably decoupling, similar those found in kinetically constrained lattice models structural glasses....

Understanding how different classes of molecules move across biological membranes is a prerequisite to predicting solute's permeation rate, which critical factor in the fields drug design and pharmacology. We use biased molecular dynamics computer simulations calculate compare free energy profiles translocation several small 1,2-dioleoyl- sn-glycero-3-phosphocholine (DOPC) lipid bilayers as first step toward determining most efficient method for calculations. study arginine, sodium ion,...

Understanding the (de)mixing behavior of multicomponent lipid bilayers is an important step towards unraveling nature spatial composition heterogeneities in cellular membranes and their role biological function. We use coarse-grained molecular dynamics simulations to study phase diagram a quaternary mixture phospholipids cholesterol. This known exhibit both uniform coexisting phases. compare combine different statistical measures membrane structure identify onset coexistence space. An...

Cells require oligonucleotides and polypeptides with specific, homochiral sequences to perform essential functions, but it is unclear how such oligomers were selected from random at the origin of life. probably preceded by simple compartments as fatty acid vesicles, that increased stability, growth, or division vesicles could have thereby in frequency. We therefore tested whether prebiotic peptides alter stability growth composed a acid. find three 15 dipeptides reduce salt-induced...

Successful theories of phase transformation processes include classical nucleation theory, which envisions a local equilibrium between coexisting phases, and nonequilibrium kinetic cluster theories. Using computer simulations the magnetization reversal Ising model in three different ensembles we make quantitative connections these physical pictures. We show that critical nucleus size theory is strongly correlated with dynamical measure metastability, metastable persists to thermodynamic...

Double-stranded DNA may contain mismatched base pairs beyond the Watson–Crick pairs, guanine–cytosine and adenine–thymine. Such mismatches bear adverse consequences for human health. We utilize molecular dynamics metadynamics computer simulations to study structure of both matched pairs. discover significant differences between in flip work profiles. Mismatched shift more plane normal strand exhibit noncanonical structures, including e-motif. discuss potential implications on mismatch repair...

Abstract Background Markov state models have been widely used to study conformational changes of biological macromolecules. These are built from short timescale simulations and then propagated extract long dynamics. However, the solvent information in molecular often ignored current methods, because large number molecules a system indistinguishability upon their exchange. Methods We present signature that compactly summarizes distribution high-dimensional data, define distance metric between...

Solvation of small and large clusters are studied by simulation, considering a range solvent−solute attractive energy strengths. Over wide conditions, both for solvation in the Lennard-Jones liquid SPC model water, it is shown that mean solvent density varies linearly with changes adhesion or strength. This behavior understood from perspective Weeks' theory (Annu. Rev. Phys. Chem. 2002, 53, 533) supports theories based upon perspective.

We present a simple, and physically motivated, coarse-grained model of lipid bilayer, suited for micron scale computer simulations. Each ~25 nm^2 patch bilayer is represented by spherical particle. Mimicking forces hydrophobic association, multi-particle interactions suppress the exposure each sphere's equator to its implicit solvent surroundings. The requirement high equatorial density stabilizes two-dimensional structures without necessitating crystalline order, allowing us match both...

We study the phase behavior of multicomponent lipid bilayer vesicles that can exhibit intriguing morphological patterns and lateral separation. use a modified Landau-Ginzburg model capable describing spatially uniform phases, microemulsions, modulated phases on spherical surface. calculate its diagram for multiple vesicle sizes using analytical numerical techniques as well Monte Carlo simulations. Consistent with previous studies planar systems, we find thermal fluctuations move boundaries,...

Membrane-induced interactions can play a significant role in the spatial distribution of membrane-bound proteins. We develop model that combines continuum description lipid bilayers with discrete particle proteins to probe emerging structure combined membrane-protein system. Our takes into account membrane's elastic behavior, steric repulsion between proteins, and quenching membrane shape fluctuations due presence employ coupled Langevin equations describe dynamics show coupling induces an...