An Accurate Prediction of Hydration Free Energies by Combination of Molecular Integral Equations Theory with Structural Descriptors

Abstract

In this work, we report a novel method for the estimation of the hydration free energy of organic molecules, the structural descriptors correction (SDC) model. The method is based on a combination of the reference interaction site model (RISM) with several empirical corrections. The model requires only a small number of chemical descriptors associated with the main features of the chemical structure of solutes: excluded volume, branch, double bond, benzene ring, hydroxyl group, halogen atom, aldehyde group, ketone group, ether group, and phenol fragment. The optimum model was selected after testing of different RISM free energy expressions on a training set of 65 molecules. We show that the correction parameters of the SDC model are transferable between different chemical classes, which allows one to cover a wide range of organic solutes. The new model substantially increases the accuracy of calculated HFEs by RISM giving the standard deviation of the error for a test set of 120 organic molecules around 1.2 kcal/mol.

Solvation Thermodynamics of Organic Molecules by the Molecular Integral Equation Theory: Approaching Chemical Accuracy

“…[85][86][87][88][89][90][91][92] 96 blind HFE challenges that provoked a wave of interest in HFE predictions using different computational techniques. These works contain several benchmark data sets that can be used for verifying new models.…”

“…2,92,313 The unifying factor in these models is that they include some empirical corrections obtained by fitting against the error ε between calculated SFEs and experimental data:…”

“…Figure 13 shows the comparison analysis of the accuracy of HFEs calculated with different 1D RISM free energy functionals. 92 The however, the authors recommend that for "simple" solutes the 1D RISM/SDC model should be used with OPLS partial charges, which are sufficient to give HFEs with small bias with respect to experimental data and a standard deviation of about 0.5 kcal/mol (see Figure 14). In the case of aromatic solutes, however, the QM-derived partial charges are more suitable since they are sensitive to the electron-donating/withdrawing nature of substituents, whereas the OPLS partial charges do not so accurately reflect these details.…”

Electrostatic interactions in biological DNA-related systems

“…Arg was claimed to be preferred over Lys in the minor grooves because of a lower self-energy cost to remove a larger guanidinium group of Arg + from its hydrated state in solution and bring it in contact to the DNA, than to do the same for a smaller ammonium group of the Lys + residue. 263 The reason is the Born ES self-energy that scales inversely proportional to the ''ion'' radius [264][265][266][267][268] (see also recent numerical studies on the hydration of small organic molecules 269,270 and polypeptides [271][272][273] ). Being valid for large structural complexes, the ES complementarity recognition model however fails for small DNAprotein complexes, with simple standard motifs of DNA recognition (e.g., helix-turn-helix, zinc finger, and leucine zipper).…”

Communication: Long-range angular correlations in liquid water

“…11 The entire DFT calculation takes about 12 h in one desktop computer with 3.0 GHz CPU. Because the above procedure involves only iteration for the three-dimensional calculations and the six-dimensional density profile is calculated as an output, our numerical procedure is much more efficient than that for the molecular Ornstein-Zernike (MOZ) theory 15,16 and that in direct multi-dimensional DFT calculations. 17,18 The DFT predicts the atom-atom RDFs (see Figure S1 of the supplementary material 19 ) similar to those obtained from diffraction experiments, integral-equation theories, and molecular simulations.…”