Free energy profiles of amino acid side chain analogs near water‐vapor interface obtained via MD simulations

Abstract

Solvation of 13 neutral amino acid side chain analogs at water-vapor interface was studied by computing high precision free energy profiles of the molecules across the interface using molecular dynamics (MD) simulations. The SPC water model (Berendsen, H. J. C., Postma, J. P. M., van Gunsteren, W. F., Hermans, P. A. K. J., Dixon, R., Cornell, W., Fox, T., Chipot, C., Pohorille, A. In: Wilkinson, A., Weiner, P. and van Gunsteren, W. F. editors. Intermolecular Forces, 1981, 3, 331) and OPLS-AA (Jorgensen et al., J Am Chem Soc, 1996, 118, 11225) potential parameter sets were used. A rigorous approach for the computation of high precision free energy profiles at water-vapor interface using constraint force technique is implemented. Methodology of obtaining high precision potential of mean force (PMF) profiles free of simulation artifacts in MD simulations is outlined and discussed. The accuracy of the calculations is examined by comparing the hydration free energies of studied solutes obtained from PMF calculations and separately using Bennett acceptance ratio technique by decoupling solvent-solute interactions in the bulk. All molecules exhibit a free energy minimum at interface. No significant desolvation barrier is observed for any of the studied species. Adsorption energies for studied molecules at water-vapor interface are estimated and compared with experimental observations. We find that for modeled neutral compounds pronounced surface influence on solute solvation vanishes already at 6-7 A behind the water surface as the solvation free energy approaches the bulk value. The possibility of force field refinement using adsorption free energies is outlined.

Water models for biomolecular simulations

“…The PB or the GB models are only linear‐response, mean‐field, continuum dielectric approximations to the many‐body problem of electrostatic interactions in a solute‐solvent system, with solute molecules being of finite size. A hierarchy of approximations, many of which are essentially unavoidable, separates the PB (and the GB) from the more fundamental explicit solvent representation, and from reality . These approximations result in notable limitations of the pure GB or PB frameworks, such as their inability to account for many prominent explicit solvent effects, including charge hydration asymmetry and other water multipole effects, water ‘bridges,’ electrostriction and dielectric saturation .…”

Calculation of the Intrinsic Solvation Free Energy Profile of an Ionic Penetrant Across a Liquid–Liquid Interface with Computer Simulations

“…To circumvent this problem, several methods providing enhanced sampling of rare events, such as harmonic and adaptive umbrella sampling, thermodynamic integration, metadynamics, , the Widom test particle insertion method and its cavity insertion variant, or potential of mean force (PMF) calculation by, for example, constrained molecular dynamics, , have been proposed over the years. These methods of solvation free energy calculation have been applied for a number of ionic − and nonionic penetrants ,− at various fluid interfaces in the past decades, complementing theoretical predictions based on various continuum dielectric calculations. , …”

Calculation of the intrinsic solvation free energy profile of methane across a liquid/liquid interface in computer simulations

“…these methods have been widely used for a number of non-ionic [19][20][21][22][23][24][25][26][27][28] and ionic penetrants [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] at various fluid interfaces.…”