A theoretical databank of transferable aspherical atoms and its application to electrostatic interaction energy calculations of macromolecules

A comprehensive version of the theoretical databank of transferable aspherical pseudoatoms is described, and its first application to protein-ligand interaction energies is discussed. The databank contains all atom types present in natural amino acid residues and other biologically relevant molecules. Each atom type results from averaging over a family of chemically unique pseudoatoms, taking into account both first and second neighbors. The spawning procedure is used to ensure that close transferability is obeyed. The databank is applied to the syntenin PDZ2 domain complexed with four-residue peptides and to the PDZ2 dimer. Analysis of the electrostatic interactions energies calculated by the exact-potential/multipole-moment-databank method stresses the importance of the P-0 and P-2 residues of the peptide in establishing the interaction, whereas the P-1 residue is shown to play a much smaller role. Unexpectedly, the charged P-3 residue contributes significantly to the interaction. The class I and II peptides are bound with the same strength by the syntenin PDZ2 domain, though the electrostatic interaction energy of the P-2 residue is smaller for class I peptides. There is no difference between the interaction energies of the peptides with PDZ2 domains from single-domain protein fragments and those from PDZ1-PDZ2 tandems.