Ligand Docking Benchmark in Rosetta using Explicitly Placed Atomic Orbitals

Abstract

Protein-ligand interactions are important in a variety of biological areas. The strength and location of these interactions is driven by Partial Covalent Interactions between the protein and ligand. The Rosetta framework has been updated to explicitly capture and score these interactions. A ligand docking benchmark using this procedure performs between ten and fifteen percent better than the previous procedure performs. Explicit placement of atomic orbitals was used to capture the interactions. Orbitals were placed using hybridization information consistent with quantum chemical calculations performed on the same benchmark set. A statistical model over 8000 high resolution crystal structures was generated in order to score hydrogen bonding interactions, cation-pi interactions, and pi-pi interactions. In most cases, important binding interactions were captured.