Ionizable residues play important roles in protein structure and activity, and proton binding is a valuable reporter of electrostatic interactions in these systems. We use molecular dynamics free energy simulations (MDFE) to compute proton pKa shifts, relative to a model compound in solution, for three aspartate side chains in two proteins. Simulations with explicit solvent and with an implicit...

Implicit algorithms work on their input’s characteristic functions and should solve problems heuristically by as few and as efficient functional operations as possible. Together with an appropriate data structure to represent the characteristic functions they yield heuristics which are successfully applied in numerous areas. It is known that implicit algorithms which execute t(N) functional ope...

Physiological solvent flows surround biological structures triggering therein collective motions. Notable examples are virus/host-cell interactions and solvent-mediated allosteric regulation. The present work describes a multiscale approach joining the Lattice Boltzmann fluid dynamics (for flows) with all-atom atomistic molecular proteins) to model functional between molecules. We present, as a...

We present an implicit solvent model based on the extended reference interaction site model (XRISM) integral equation theory, which is a molecular theory of solvation. The solvation free energy is composed of additive potentials of mean force (PMF) of various functional groups. The XRISM theory is applied to determine the PMF of each group in water and NaBr electrolyte solutions. The method has...

The central importance of solvent interactions in stabilization of specific protein structure has long been recognized. Decades ago, Tanford and Kirkwood treated in detail the interaction of charges with solvent, and they showed how desolvation/burial of charges upon protein folding was an important factor in stability.1 The influence of their model, with further elaborations, can still be seen...

Theoretical justification for preferential heterochiral cyclic trimerization of 5-(aminoethyl)-2-furancarboxylic acid (AEFC) is attempted using density functional theory (DFT) calculations. Results from explicit solvent assisted reaction pathways indicate greater stability of heterochiral cyclic tripeptides over their homochiral counterparts, contrary to findings from gas phase and implicit sol...

A semi-implicit orbit-averaged time-integration algorithm has been successfully implemented in a gyrokinetic particle simulation code for the study of self-consistent phenomena in a strongly magnetized plasma. The semi-implicit aspect of the integration scheme relaxes the timestep constraints required to insure numerical stability. The orbit averaging is useful in reducing statistical noise and...

Recent progress in modelling the solvent vapor annealing of thin film block copolymers is examined in the context of a self-consistent field theory framework. Key control variables in determining the final microdomain morphologies include swelling ratio or swollen film solvent volume fraction, swollen film thickness, substrate and vapor atmosphere surface energies, effective volume fraction, an...

The non-polar component of the potential of mean force of dimerization of alanine dipeptide has been calculated in explicit solvent by free energy perturbation. We observe that the calculated PMF is inconsistent with a non-polar hydration free energy model based solely on the solute surface area. The non-linear behavior of the solute-solvent van der Waals energy is primarily responsible for the...

Atomic radii and charges are two major parameters used in implicit solvent electrostatics and energy calculations. The optimization problem for charges and radii is underdetermined, leading to uncertainty in the values of these parameters and in the results of solvation energy calculations using these parameters. This paper presents a new method for quantifying this uncertainty in implicit solv...