Solvation Model Based on Weighted Solvent Accessible Surface Area

Abstract

We have developed a fast procedure to predict solvation free energies for both organic and biological molecules. This solvation model is based on weighted solvent accessible surface area (WSAS). Least-squares fittings have been applied to optimize the weights of SAS for different atom types in order to reproduce the experimental solvation free energies. Good agreement with experimental results has been obtained. For the 184-molecule set (model I), for which there are experimental solvation free energies in 1-octanol, we have achieved an average error of 0.36 kcal/mol, better than that of the SM5.42R universal solvation model 1 by Li et al. For the 245-molecule set (model II) that has experimental aqueous solvation free energies, our WSAS model achieves an average error of 0.48 kcal/mol, marginally larger than that of Li's model (0.46 kcal/mol). We have used a 401-molecule set, the largest training set (model IV) that we know of solvation model development, to derive the SAS weights in order to reproduce the experimental solvation free energies in water. For this model, we have achieved an average unsigned error of 0.54 kcal/mol and an RMS error of 0.79 kcal/mol.The advantage of this model lies in its simplicity and independence of charge models. We have successfully applied this model to predict the relative binding free energies for the five binding modes of HIV-1RT/ efavirenz. The most favorable binding mode, which has an RMSD of 1.1 Å (for 54 C R around the binding site) compared to the crystal structure, has a binding free energy at least 10 kcal/mol more negative than the other binding modes. Moreover, the solvation free energies with WSAS have a high correlation (the correlation coefficient is 0.92) to the solvation free energies calculated by the Poisson-Boltzmann/surface area (PBSA) model. As an efficient and fast approach, WASA is also attractive for protein modeling and protein folding studies. We have applied this model to predict the solvation free energies of the 36-mer villin headpiece subdomain in its native structure, a compact folding intermediate, and a random coil. The rank order of the solvation free energies and the free energies for the three kinds of conformational clusters are in reasonable agreement with those found by MM-PBSA, a widely used solvation free energy model.

On the transferability of hydration‐parametrized continuum electrostatics models to solvated binding calculations

“…15 These experimental hydration free energies range from Ϫ10.92 to 2.89 kcal/mol, with a mean Ϯ standard deviation (SD) of Ϫ3.29 Ϯ 2.67 kcal/mol. Molecular geometries were generated using CONCORD.…”

Efficient factors in protein modification: ADenosine deaminase esterification by woodward reagent K

“…It is apparent that the evaluation of relative stability of the above species requires to take an entropic quantitative into account. As stated elsewhere, empirical WASA models can be used in hydration free energy calculations with reasonable precision and an error of less than 1 kcal mol -1 [18]. Nevertheless, these methods have a minor computational cost compared to free energy perturbation techniques.…”

“…A WASA model was employed to determine hydration free energies [18]. Gaussian 98 program revision A-9 [32] was used for energy calculation using the B3LYP/6-31G* method [33,34].…”

“…In this study, a full ASA model is employed to obtain relative stability of modified ADA as well as transition states arising in the modification of ADA [18]. As stated elsewhere [18], atomic free energies of the latter model are determined by employing a large data set.…”

“…As stated elsewhere [18], atomic free energies of the latter model are determined by employing a large data set. In this model, atom types outnumber other ASA models [10,19] and thus have considerable flexibility in evaluation of hydration free energies.…”