A knowledge-based scoring function to assess quaternary associations of proteins.

MOTIVATION: The elucidation of all inter-protein interactions would significantly enhance our knowledge of cellular processes at a molecular level. Given the enormity of the problem, the expenses and limitations of experimental methods, it is imperative that this problem is tackled computationally. In silico predictions of protein interactions entail sampling different conformations of the purported complex and then scoring these to assess for interaction viability. In this study, we have devised a new scheme for scoring protein-protein interactions. RESULTS: Our method, PIZSA (Protein Interaction Z-Score Assessment), is a binary classification scheme for identification of native protein quaternary assemblies (binders/nonbinders) based on statistical potentials. The scoring scheme incorporates residue-residue contact preference on the interface with per residue-pair atomic contributions and accounts for clashes. PIZSA can accurately discriminate between native and non-native structural conformations from protein docking experiments and outperform other contact-based potential scoring functions. The method has been extensively benchmarked and is among the top 6 methods, outperforming 31 other statistical, physics based and machine learning scoring schemes. The PIZSA potentials can also distinguish crystallization artifacts from biological interactions. AVAILABILITY AND IMPLEMENTATION: PIZSA is implemented as a web server at http://cospi.iiserpune.ac.in/pizsa and can be downloaded as a standalone package from http://cospi.iiserpune.ac.in/pizsa/Download/Download.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Protein Interaction Z Score Assessment (PIZSA): an empirical scoring scheme for evaluation of protein-protein interactions.

Our web server, PIZSA (http://cospi.iiserpune.ac.in/pizsa), assesses the likelihood of protein-protein interactions by assigning a Z Score computed from interface residue contacts. Our score takes into account the optimal number of atoms that mediate the interaction between pairs of residues and whether these contacts emanate from the main chain or side chain. We tested the score on 174 native interactions for which 100 decoys each were constructed using ZDOCK. The native structure scored better than any of the decoys in 146 cases and was able to rank within the 95th percentile in 162 cases. This easily outperforms a competing method, CIPS. We also benchmarked our scoring scheme on 15 targets from the CAPRI dataset and found that our method had results comparable to that of CIPS. Further, our method is able to analyse higher order protein complexes without the need to explicitly identify chains as receptors or ligands. The PIZSA server is easy to use and could be used to score any input three-dimensional structure and provide a residue pair-wise break up of the results. Attractively, our server offers a platform for users to upload their own potentials and could serve as an ideal testing ground for this class of scoring schemes.