Optimized distance-dependent atom-pair-based potential DOOP for protein structure prediction

ABSTRACT The DOcking decoy‐based Optimized Potential (DOOP) energy function for protein structure prediction is based on empirical distance‐dependent atom‐pair interactions. To optimize the atom‐pair interactions, native protein structures are decomposed into polypeptide chain segments that correspond to structural motives involving complete secondary structure elements. They constitute near native ligand–receptor systems (or just pairs). Thus, a total of 8609 ligand–receptor systems were prepared from 954 selected proteins. For each of these hypothetical ligand–receptor systems, 1000 evenly sampled docking decoys with 0–10 Å interface root‐mean‐square‐deviation (iRMSD) were generated with a method used before for protein–protein docking. A neural network‐based optimization method was applied to derive the optimized energy parameters using these decoys so that the energy function mimics the funnel‐like energy landscape for the interaction between these hypothetical ligand–receptor systems. Thus, our method hierarchically models the overall funnel‐like energy landscape of native protein structures. The resulting energy function was tested on several commonly used decoy sets for native protein structure recognition and compared with other statistical potentials. In combination with a torsion potential term which describes the local conformational preference, the atom‐pair‐based potential outperforms other reported statistical energy functions in correct ranking of native protein structures for a variety of decoy sets. This is especially the case for the most challenging ROSETTA decoy set, although it does not take into account side chain orientation‐dependence explicitly. The DOOP energy function for protein structure prediction, the underlying database of protein structures with hypothetical ligand–receptor systems and their decoys are freely available at http://agknapp.chemie.fu‐berlin.de/doop/. Proteins 2015; 83:881–890. © 2015 Wiley Periodicals, Inc.