Detailed ab initio prediction of lysozyme–antibody complex with 1.6 Å accuracy

Abstract

The fundamental event in biological assembly is association of two biological macromolecules. Here we present a successful, accurate ab initio prediction of the binding of uncomplexed lysozyme to the HyHel5 antibody. The prediction combines pseudo Brownian Monte Carlo minimization with a biased-probability global side-chain placement procedure. It was effected in an all-atom representation, with ECEPP/2 potentials complemented with the surface energy, side-chain entropy and electrostatic polarization free energy. The near-native solution found was surprisingly close to the crystallographic structure (root-mean-square deviation of 1.57 A for all backbone atoms of lysozyme) and had a considerably lower energy (by 20 kcal mol-1) than any other solution.