Are hydrodynamic interactions important in the kinetics of hydrophobic collapse?

We study the kinetics of assembly of two plates of varying hydrophobicity, including cases where drying occurs and water strongly solvates the plate surfaces. The potential of mean force and molecular-scale hydrodynamics are computed from molecular dynamics simulations in explicit solvent as a function of particle separation. In agreement with our recent work on nanospheres [J. Phys. Chem. B 116, 378 (2012)] regions of high friction are found to be engendered by large and slow solvent fluctuations. These slow fluctuations can be due to either drying or confinement. The mean first passage times for assembly are computed by means of molecular dynamics simulations in explicit solvent and by Brownian dynamics simulations along the reaction path. Brownian dynamics makes use of the potential of mean force and hydrodynamic profile that we determined. Surprisingly, we find reasonable agreement between full scale molecular dynamics and Brownian dynamics, despite the role of slow solvent relaxation in the assembly process. We found that molecular scale hydrodynamic interactions are essential in describing the kinetics of assembly.Comment: 6 figures, 13 page

Self-diffusion in two-dimensional hard ellipsoid suspensions

We studied the self-diffusion of colloidal ellipsoids in a monolayer near a flat wall by video microscopy. The image processing algorithm can track the positions and orientations of ellipsoids with sub-pixel resolution. The translational and rotational diffusions were measured in both the lab frame and the body frame along the long and short axes. The long-time and short-time diffusion coefficients of translational and rotational motions were measured as functions of the particle concentration. We observed sub-diffusive behavior in the intermediate time regime due to the caging of neighboring particles. Both the beginning and the ending times of the intermediate regime exhibit power-law dependence on concentration. The long-time and short-time diffusion anisotropies change non-monotonically with concentration and reach minima in the semi-dilute regime because the motions along long axes are caged at lower concentrations than the motions along short axes. The effective diffusion coefficients change with time t as a linear function of (lnt)/t for the translational and rotational diffusions at various particle densities. This indicates that their relaxation functions decay according to 1/t which provides new challenges in theory. The effects of coupling between rotational and translational Brownian motions were demonstrated and the two time scales corresponding to anisotropic particle shape and anisotropic neighboring environment were measured

The role of water and steric constraints in the kinetics of cavity-ligand unbinding

A key factor influencing a drug's efficacy is its residence time in the binding pocket of the host protein. Using atomistic computer simulation to predict this residence time and the associated dissociation process is a desirable but extremely difficult task due to the long timescales involved. This gets further complicated by the presence of biophysical factors such as steric and solvation effects. In this work, we perform molecular dynamics (MD) simulations of the unbinding of a popular prototypical hydrophobic cavity-ligand system using a metadynamics based approach that allows direct assessment of kinetic pathways and parameters. When constrained to move in an axial manner, we find the unbinding time to be on the order of 4000 sec. In accordance with previous studies, we find that the ligand must pass through a region of sharp dewetting transition manifested by sudden and high fluctuations in solvent density in the cavity. When we remove the steric constraints on ligand, the unbinding happens predominantly by an alternate pathway, where the unbinding becomes 20 times faster, and the sharp dewetting transition instead becomes continuous. We validate the unbinding timescales from metadynamics through a Poisson analysis, and by comparison through detailed balance to binding timescale estimates from unbiased MD. This work demonstrates that enhanced sampling can be used to perform explicit solvent molecular dynamics studies at timescales previously unattainable, obtaining direct and reliable pictures of the underlying physio-chemical factors including free energies and rate constants.Comment: 7 pages, 4 figures, supplementary PDF file, submitte