Ranking multiple docking solutions based on the conservation of inter-residue contacts

Authors

  • Romina Oliva,

    Corresponding author
    1. Department of Applied Sciences, University “Parthenope” of Naples, Centro Direzionale Isola C4, Naples, Italy
    • Correspondence to: Romina Oliva; Department of Applied Sciences, University “Parthenope” of Naples, Centro Direzionale Isola C4 80143, Naples, Italy; E-mail: romina.oliva@uniparthenope.it

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  • Anna Vangone,

    1. Department of Chemistry and Biology, University of Salerno, Via ponte don Melillo, Fisciano, (SA), Italy
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  • Luigi Cavallo

    1. Department of Chemistry and Biology, University of Salerno, Via ponte don Melillo, Fisciano, (SA), Italy
    2. KAUST Catalysis Center (KCC), King Abdullah University of Science & Technology, Saudi Arabia
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ABSTRACT

Molecular docking is the method of choice for investigating the molecular basis of recognition in a large number of functional protein complexes. However, correctly scoring the obtained docking solutions (decoys) to rank native-like (NL) conformations in the top positions is still an open problem. Herein we present CONSRANK, a simple and effective tool to rank multiple docking solutions, which relies on the conservation of inter-residue contacts in the analyzed decoys ensemble. First it calculates a conservation rate for each inter-residue contact, then it ranks decoys according to their ability to match the more frequently observed contacts. We applied CONSRANK to 102 targets from three different benchmarks, RosettaDock, DOCKGROUND, and Critical Assessment of PRedicted Interactions (CAPRI). The method performs consistently well, both in terms of NL solutions ranked in the top positions and of values of the area under the receiver operating characteristic curve. Its ideal application is to solutions coming from different docking programs and procedures, as in the case of CAPRI targets. For all the analyzed CAPRI targets where a comparison is feasible, CONSRANK outperforms the CAPRI scorers. The fraction of NL solutions in the top ten positions in the RosettaDock, DOCKGROUND, and CAPRI benchmarks is enriched on average by a factor of 3.0, 1.9, and 9.9, respectively. Interestingly, CONSRANK is also able to specifically single out the high/medium quality (HMQ) solutions from the docking decoys ensemble: it ranks 46.2 and 70.8% of the total HMQ solutions available for the RosettaDock and CAPRI targets, respectively, within the top 20 positions. Proteins 2013. © 2013 Wiley Periodicals, Inc.

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