Large-scale DFT calculations in implicit solvent-A case study on the T4 lysozyme L99A/M102Q protein

• Published in: International journal of quantum chemistry Vol. 113; no. 6; pp. 771 - 785
• Main Authors: Dziedzic, Jacek, Fox, Stephen J., Fox, Thomas, Tautermann, Christofer S., Skylaris, Chris-Kriton
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.03.2013; Wiley Subscription Services, Inc
• Subjects: Chemistry; DFT; implicit solvent; ONETEP; Physical chemistry; Quantum physics
• ISSN: 0020-7608; 1097-461X
• DOI: 10.1002/qua.24075

Recently, variants of implicit solvation models for first principles electronic structure calculations based on a direct solution of the nonhomogeneous Poisson equation in real space have been developed. These implicit solvation models are very elegant from a physical point of view as the solute cavity is defined directly via isosurfaces of the electronic density, and the molecular charge is polarized self‐consistently by the reaction field of the dielectric continuum which surrounds the solute. Nevertheless, the implementation of these models is technically complex and requires great care. A certain level of care is required from users of such models as a number of numerical parameters need to be given appropriate values to obtain the most accurate and physically relevant results. Here, we describe in what parts of the solvent model each of these numerical parameters is involved and present a detailed study of how they can affect the calculation, using the solvation model which has been implemented in the ONETEP program for linear‐scaling density functional theory (DFT) calculations. As ONETEP is capable of DFT calculations with thousands of atoms, we focus our investigation of the numerical parameters with a case study on protein–ligand complexes of the entire 2602‐atom T4 Lysozyme L99/M102Q protein. We examine effects on solvation energies and binding energies, which are critical quantities for computational drug optimization and other types of biomolecular simulations. We propose optimal choices of these parameters suitable for routine “production” calculations. © 2012 Wiley Periodicals, Inc. When employing implicit solvation models great care is required in the selection of a number of numerical parameters in order to obtain accurate and physically relevant results. This article presents a detailed study of how these parameters can affect the calculation of solvation and binding energies of large biomolecules in solution and provides a recipe for their optimal selection for routine “production” calculations.