Molecular dynamics simulations of ionic and nonionic surfactant micelles with a generalized born implicit‐solvent model

Abstract

In recent years, all-atom and coarse-grained models have been developed and applied to simulations of micelles and biological membranes. Here, we explore the question of whether a combined all-atom representation of surfactant molecules and continuum description of solvent based on the generalized Born model can be used to study surfactant micelles. Specifically, we report the parameterization of the GBSW model with a surface-area dependent nonpolar solvation energy term for dodecyl sulfate, dodecyl tetramethylammonium, and dodecyl triethyleneglycol ether molecules. In the parameterization procedure,the atomic Born radii were derived from the radial distribution functions of solvent charge and refined targeting the potential of mean force of dimer interactions from explicit-solvent simulations. The optimized radii were then applied in molecular dynamics simulations of the ionic and nonionic micelles.We found that the micelles are stable but more compact and rigid than in explicit solvent as a consequence of the drastic reduction in solvation and mobility of surfactant monomers within the micelle. Based on these data and our previous work, we suggest that in addition to a more accurate description of the nonpolar solvation energy, the ruggedness in the short-range interactions due to solvent granularity is a critical feature that needs to be taken into account to accurately model processes such as micelle formation and protein folding in implicit solvent. Finally, the explicit-solvent data presented here offers new insights into different conformational behavior of ionic and nonionic micelles which is valuable for understanding hydrophobic assemblies and of interest to the detergent industry.

Recent development and application of constant pH molecular dynamics

“…Although the calculation agreed well with experiment for the anionic and neutral micelles, the calculated p K a shift was in the wrong direction for a cationic micelle, where the balance between electrostatic stabilization and desolvation is biased towards the former [27]. We attributed the discrepancy to the micelle being more compact and rigid in the GB-based conformational sampling [42, 27]. Indeed, using the hybrid-solvent pHREX-CpHMD, which utilizes explicit-solvent model for conformational sampling, the calculated p K a shift was greatly improved [27].…”

Toward accurate prediction of pKa values for internal protein residues: The importance of conformational relaxation and desolvation energy

“…Although adjustment of the solute‐solvent dielectric boundary can largely reduce errors in the description of solvent‐mediated interactions, there is a limit to the improvement using the current forms of GB models, as demonstrated previously by others35 and recently by us 40. This aspect can be sensitively tested in the p K a calculations of solvent‐exposed residues or those close to the solute‐solvent interface using GB‐based CPHMD simulations.…”

Charge-leveling and proper treatment of long-range electrostatics in all-atom molecular dynamics at constant pH

“…It can be seen that the deprotonation free energy with the GB model is about 10 kcal/mol (or 20%) smaller than with the explicit-solvent model, indicating that the charged form is less favored by the GB model, consistent with our observation that solvation energies in GB simulations are underestimated. 47 …”