A new method to determine electrostatic potential around a macromolecule in solution from molecular wave functions

<jats:title>Abstract</jats:title><jats:p>The three‐dimensional reference interaction site model integral equation theory (3D‐RISM) combined with the <jats:italic>ab initio</jats:italic> molecular orbital method (3D‐RISM‐SCF) is applied to a solvated macromolecular system. The solvation structure around a solute molecule is obtained from the 3D‐RISM integral equation under the electrostatic potential of the solute molecule, calculated by the <jats:italic>ab initio</jats:italic> molecular orbital theory. The electrostatic potential should be calculated on each grid point in the three‐dimensional real space. Therefore, the calculation of the electrostatic potential is the most time consuming part in this method. In this article, we propose a new procedure to save the computational cost for calculating the electrostatic potential and the solvated fock matrix. The strategy of this procedure is to evaluate the electrostatic potential and the solvated fock matrix in different ways, depending on the distance between solute and solvent. Inside the repulsive cores of solute atoms, it is possible to avoid the calculation of electrostatic potential and solvated Fock matrix by assuming the potential to be infinity. In the region sufficiently far from solute, they are evaluated classically by putting the effective point charge on each atom. In the intermediate region, the electrostatic potential is evaluated directly by integrating the molecular orbitals of the solute molecule. The electronic structure and the energy gradient of Methionine‐Enkephalin and solvation structure are estimated by using this procedure in aqueous solution, and are compared with the results from other procedures. The results are compared also with those from the continuum model. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 453–462, 2006</jats:p>