Noncovalent Interactions in Solvated Proteins and Protein Crystals Studied with the Fragment Molecular Orbital Method

A new formulation of the many-body expansion of the electron density expressed in terms of the wave function data is developed in the framework of the fragment molecular orbital (FMO) method for the purpose of visualizing noncovalent interactions (NCI) in large systems. This expansion can also be used for a selected site of interest, such as a ligand binding site in a protein. The site formulation is shown to be both accurate and efficient, as demonstrated for a small protein-ligand complex (Trp-cage protein, PDB: 1L2Y) and a large complex of prostaglandin H2 synthase-1 (1EQG) with ibuprofen. In addition, the FMO/NCI methodology is extended to treat periodic boundary conditions, with an application to study packing effects in the crystal of crambin (1CBN).