EnCPdock: a web-interface for direct conjoint comparative analyses of complementarity and binding energetics in inter-protein associations
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Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.26.530084v1?rss=1

Authors: Biswas, G., Mukherjee, D., Dutta, N., Ghosh, P., Basu, S.

Abstract: Protein-protein interaction (PPI) is a key component linked to virtually all cellular processes. Be it an enzyme catalysis (classic type functions of proteins) or a signal transduction (non-classic), proteins generally function involving stable or quasi-stable multi-protein associations. The physical basis for such associations is inherent in the combined effect of shape and electrostatic complementarities (Sc, EC) of the interacting protein partners at their interface. While Sc is a necessary criterion for inter-protein associations, EC can be favorable as well as disfavored (e.g., in transient interactions). Estimating equilibrium thermodynamic parameters (delta Gbinding, Kd) by experimental means is costly and time consuming, thereby opening windows for computational structural interventions. Attempts to empirically probe delta_G_binding from coarse-grain structural descriptors (primarily, surface area based terms) have lately been overtaken by physics-based, knowledge-based and their hybrid approaches (MM/PBSA, FoldX etc.) that directly compute delta_G_binding without involving intermediate structural descriptors. Here we present EnCPdock (www.scinetmol.in/EnCPdock/), a user-friendly web-interface for the direct conjoint comparative analyses of complementarity and binding energetics in proteins. EnCPdock returns an AI-predicted delta_G_binding computed by combining complementarity (Sc, EC) and other high-level structural terms, and, renders a prediction accuracy comparable to the state-of-the-art. EnCPdock further locates a PPI complex in terms of its {Sc, EC} values (taken as an ordered pair) in the two-dimensional Complementarity Plot (CP). In addition, it also generates mobile molecular graphics of the interfacial atomic contact network. Combining all its features, EnCPdock presents a unique online tool that should be beneficial to structural biologists and researchers across related fraternities.

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