Importance of Charge Balance for the Embedding of Zwitterionic Solutes in the Fragment Molecular Orbital Method.

Abstract

Three new schemes of induced solvent charges for the auxiliary polarization formulation of the fragment molecular orbital method are proposed and compared to the original approach. It is found that the charge balance of the solute and solvent embeddings is crucial for maintaining a proper gap between occupied and virtual orbitals of fragments for zwitterionic systems in solution. The original instability is eliminated with the new scheme of fragment-specific solvent charges. The developed stable embedding method is applied to perform MP2/aug-cc-pVTZ calculations of a protein-ligand complex containing 1102 amino acid residues.