igorb@bii.a-star.edu.sg.

The AlloSigMA 2 server provides an interactive platform for exploring the allosteric signaling caused by ligand binding and/or mutations, for analyzing the allosteric effects of mutations and for detecting potential cancer drivers and pathogenic nsSNPs. It can also be used for searching latent allosteric sites and for computationally designing allosteric effectors for these sites with required agonist/antagonist activity. The server is based on the implementation of the Structure-Based Statistical Mechanical Model of Allostery (SBSMMA), which allows one to evaluate the allosteric free energy as a result of the perturbation at per-residue resolution. The Allosteric Signaling Map (ASM) providing a comprehensive residue-by-residue allosteric control over the protein activity can be obtained for any structure of interest. The Allosteric Probing Map (APM), in turn, allows one to perform the fragment-based-like computational design experiment aimed at finding leads for potential allosteric effectors. The server can be instrumental in elucidating of allosteric mechanisms and actions of allosteric mutations, and in the efforts on design of new elements of allosteric control. The server is freely available at: http://allosigma.bii.a-star.edu.sg

AlloMAPS database provides data on the causality and energetics of allosteric communication obtained with the structure-based statistical mechanical model of allostery (SBSMMA). The database contains data on allosteric signaling in three sets of proteins and protein chains: (i) 46 proteins with comprehensively annotated functional and allosteric sites; (ii) 1908 protein chains from PDBselect set of chains with low (<25%) sequence identity; (iii) 33 proteins with more than 50 known pathological SNPs in each molecule. In addition to energetics of allosteric signaling between known functional and regulatory sites, allosteric modulation caused by the binding to these sites, by SNPs, and by mutations designated by the user can be explored. Allosteric Signaling Maps (ASMs), which are produced via the exhaustive computational scanning for stabilizing and destabilizing mutations and for the modulation range caused by the sequence position are available for each protein/protein chain in the database. We propose to use this database for evaluating the effects of allosteric signaling in the search for latent regulatory sites and in the design of allosteric sites and effectors. The database is freely available at: http://allomaps.bii.a-star.edu.sg.