The detection and characterization of binding pockets and allosteric communication in proteins is crucial for studying biological regulation and performing drug design. Nowadays, ever-longer molecular dynamics (MD) simulations are routinely used to investigate the spatiotemporal evolution of proteins. In this talk, I will describe a recently presented tool, called Pocketron, that examines pocket formation, dynamics and communication embedded in microsecond-long MD simulations. This method was applied to analyse extended simulations of three pharmaceutically relevant protein systems, namely PNP, A2A, and Abl kinase. This dynamic analysis uses pocket crosstalk, defined as the temporal exchange of atoms between adjacent pockets, along the MD trajectories as a fingerprint of hidden allosteric communication networks. As a result, cryptic and transient sites were identified, paving the way for subsequent computational and/or experimental studies. Along these lines, I will exemplify the MD-Binding approach, which represents a fully dynamical docking tool that uses predefined target binding pocket for ligand screening.

Allosteric communication networks in proteins revealed through pocket Crosstalk analysis

256th National Meeting (2018)

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