Application of pyDock, CCharPPI and ConSurf to identify physiological dimers

Abstract

Trabajo presentado en 3D-BioInfo ELIXIR Community Annual Meeting, celebrado online (vía zoom), del 2 al 4 de noviembre de 2021We describe here our participation in the Activity II of the ELIXIR 3D-BioInfo Community "Open resources for sharing, integrating and benchmarking software tools for modelling the proteome in 3D". A major goal of this 3D-BioInfo activity is the application of computational tools to improve the discrimination between physiological and non-physiological dimer interfaces. With this purpose, we have applied a variety of scoring parameters to the proposed benchmark version 3, composed of 836 physiological and 841 non-physiological dimer interfaces. The scoring functions we have evaluated are: i) pyDock [1] docking score, which is composed of electrostatics, desolvation, and van der Waals energy terms (the latter weighted by 10%). This combination was optimized for the scoring of poses from ab initio docking, and seems also suitable for models generated by template-based docking. Here we will apply this function as well as each individual pyDock energy term to the proposed benchmark of dimer interfaces. ii) 88 descriptors in CCharPPI [2] (https://life.bsc.es/pid/ccharppi/). From the original 108 descriptors, we have discarded those descriptors that failed in a significant number cases. iii) Conservation score in ConSurf [3] (https://consurf.tau.ac.il/). We have applied the score to evaluate the conservation of protein-protein interface residues and provide a composite value that help to identify the physiological interfaces. We will also discuss the performance of all these descriptors on the discrimination of physiological and non-physiological dimer interfaces, and propose ways of combining these descriptors for optimal predictions. [1] Cheng TM, Blundell TL, Fernandez-Recio J (2007) Proteins 68, 503¿515. [2] Moal IH, Jiménez-García B, Fernandez-Recio J (2015) Bioinformatics 31, 123-125. [3] Glaser F, Pupko T, Paz I, Bell RE, Bechor D, Martz E, Ben-Tal N (2003) Bioinformatics 19, 163-164