New additions to the ClusPro server motivated by CAPRI

Abstract

The heavily used protein-protein docking server ClusPro performs three computational steps as follows: (1) rigid body docking, (2) RMSD based clustering of the 1000 lowest energy structures, and (3) the removal of steric clashes by energy minimization. In response to challenges encountered in recent CAPRI targets, we added three new options to ClusPro. These are (1) accounting for Small Angle X-ray Scattering (SAXS) data in docking; (2) considering pairwise interaction data as restraints; and (3) enabling discrimination between biological and crystallographic dimers. In addition, we have developed an extremely fast docking algorithm based on 5D rotational manifold FFT, and an algorithm for docking flexible peptides that include known sequence motifs. We feel that these developments will further improve the utility of ClusPro. However, CAPRI emphasized several shortcomings of the current server, including the problem of selecting the right energy parameters among the five options provided, and the problem of selecting the best models among the 10 generated for each parameter set. In addition, results convinced us that further development is needed for docking homology models. Finally we discuss the difficulties we have encountered when attempting to develop a refinement algorithm that would be computationally efficient enough for inclusion in a heavily used server.

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“…However, evaluation of all possible conformational modifications is excessively time‐consuming and computation demanding in research. Nevertheless, the majority of the ClusPro developers effort has been directed toward solving presenting flexibility or softness in the rigid‐body search and developing a scoring function that distinguishes efficiently between the correct docking solution and the lots of false positives that the search brings up this method considers the molecules as rigid objects . In the case of MD simulation, it has some inherent limitations, particularly regarding the force field accuracy.…”

“…It is one of the most widely used server for predicting antibody‐antigen interactions and ranked first in the last CAPRI (Critical Assessment of PRedicted Interactions) evaluation meeting in April 2016. Motivated by the CAPRI, through the last 2 years, ClusPro server has been substantially improved to perform ultrafast docking with considerable precision . The web server provides two platforms DOT and ZDOCK to perform rigid‐body docking and the both of which are based on the fast Fourier transform (FFT) correlation techniques.…”

“…Motivated by the CAPRI, through the last 2 years, ClusPro server has been substantially improved to perform ultrafast docking with considerable precision. 13 The web server provides two platforms DOT and ZDOCK to perform rigid-body docking and the both of which are based on the fast Fourier transform (FFT) correlation techniques. It is well accepted that FFT based algorithms are the key principle of rigid-body protein docking procedures.…”

Template‐based modeling by ClusPro in CASP13 and the potential for using co‐evolutionary information in docking

“…Features added to ClusPro, including the ability to account for Small Angle X‐ray Scattering (SAXS) profiles and pairwise distance restraints, have been motivated by specific CAPRI targets, where this information was made available to predictors. More recently, CASP‐CAPRI targets inspired the addition of a tool for the discrimination between biological and crystallographic dimers …”

“…More recently, CASP-CAPRI targets inspired the addition of a tool for the discrimination between biological and crystallographic dimers. 10 While early CAPRI targets presented participants with crystal structures for one or even both complex subunits, later rounds, including those combined with CASP rounds, have required participants to use homology models as representative subunit structures.…”