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AlloMAPS 2: allosteric fingerprints of the AlphaFold and Pfam-trRosetta predicted structures for engineering and design
AlloMAPS 2 is an update of the Allosteric Mutation Analysis and Polymorphism of Signalling database, which contains data on allosteric communication obtained for predicted structures in the AlphaFold database (AFDB) and trRosetta-predicted Pfam domains.
ReadAllosteric perspective on the mutability and druggability of the SARS-CoV-2 Spike protein
Keywords: SARS-CoV-2; Spike protein; allosteric drugs; allosteric effects of mutations; allostery; drug design; druggability; mutability.
ReadAllosteric perspective on the mutability and druggability of the SARS-CoV-2 Spike protein
Keywords: SARS-CoV-2; Spike protein; allosteric drugs; allosteric effects of mutations; allostery; drug design; druggability; mutability.
ReadDisorder driven allosteric control of protein activity
Studies of protein allostery increasingly reveal an involvement of the back and forth order-disorder transitions in this mechanism of protein activity regulation. Here, we investigate the allosteric mechanisms mediated by structural disorder using the structure-based statistical mechanical model of allostery (SBSMMA) that we have previously developed.
ReadAlloSigMA 2: paving the way to designing allosteric effectors and to exploring allosteric effects of mutations
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.
ReadOn the Allosteric Effect of nsSNPs and the Emerging Importance of Allosteric Polymorphism
The molecular mechanisms of pathological non-synonymous single-nucleotide polymorphisms are still the object of intensive research. To this end, we explore here whether non-synonymous single-nucleotide polymorphisms can work via allosteric mechanisms. Using structure-based statistical mechanical model of allostery and analyzing energetics of the effects of mutations in a set of 27 proteins with at least 50 pathological SNPs in each molecule, we found that, indeed, some SNPs can work allosterically.
ReadAlloMAPS: allosteric mutation analysis and polymorphism of signaling database
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.
ReadReversing allosteric communication: From detecting allosteric sites to inducing and tuning targeted allosteric response
The omnipresence of allosteric regulation together with the fundamental role of structural dynamics in this phenomenon have initiated a great interest to the detection of regulatory exosites and design of corresponding effectors. However, despite a general consensus on the key role of dynamics most of the earlier efforts on the prediction of allosteric sites are heavily crippled by the static nature of the underlying methods, which are either structure-based approaches seeking for deep surface pockets typical for "traditional" orthosteric drugs or sequence-based techniques exploiting the conservation of protein sequences.
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