Characteristics of Allosteric Proteins, Sites, and Modulators

Targeting a cryptic allosteric site of SIRT6 with small-molecule inhibitors that inhibit the migration of pancreatic cancer cells

“…4 C). Considering the plastic nature of allosteric pockets 41 , 42 , we further carried out MD simulation for docking optimizations, which retrieved a similar binding pose for JYQ-42 (Supporting Information Fig. S10 ).…”

Along the allostery stream: Recent advances in computational methods for allosteric drug discovery

“…For example, interactions between allosteric modulators and their sites are mainly mediated by hydrophobic interactions, which are conspicuously distinct from hydrophilic-driven orthosteric binding. 6,33,76,77,112,113 As such, traditional screening or scoring approaches for orthosteric purposes are unlikely to be capable of being expanded to allosteric investigations and deliver desirable outcomes, and might fail to pursue more accurate screening, identification, and characterization of allosteric modulators. Novel methodologies that are uniquely tailored for allosteric sites and their corresponding modulators are thus of considerable interest.…”

“…[1][2][3][4][5] Allosteric regulation is characterized by the existence of biophysical coupling between orthosteric sites and topologically distal allosteric sites, in which perturbations at allosteric sites, such as ligand binding, residue mutations, and post-translational modifications, fine-tune orthosteric sites. [6][7][8][9][10][11][12][13][14] In theory, all non-fibrous proteins are allosteric, and decades of exploration have unveiled the widespread prevalence of allosteric regulation in a plethora of biochemical and cellular events under both physiological and pathological conditions. 7,[15][16][17][18][19][20][21][22][23][24][25] Their involvement facilitates the exquisite orchestration of innumerable biological processes and is an emerging paradigm for drug discovery.…”

“…Such a concept, referred to as “allosteric regulation” or “allosterism” was further defined by Changeux et al in the 1960s 1–5 . Allosteric regulation is characterized by the existence of biophysical coupling between orthosteric sites and topologically distal allosteric sites, in which perturbations at allosteric sites, such as ligand binding, residue mutations, and post‐translational modifications, fine‐tune orthosteric sites 6–14 . In theory, all non‐fibrous proteins are allosteric, and decades of exploration have unveiled the widespread prevalence of allosteric regulation in a plethora of biochemical and cellular events under both physiological and pathological conditions 7,15–25 .…”

Allosteric pockets and dynamic residue network hubs of falcipain 2 in mutations including those linked to artemisinin resistance

“…In the most general definition, allostery is the occurrence of changes in the active site (in the case of enzyme) or binding site (in the case of receptors) due to perturbations in a topologically distal part of the protein, which is called allosteric site; and the perturbations can be due to ligands, ions or DNA/RNA binding, residue mutations or post-translational modifications [82] , [83] , [84] , [85] . Allosteric effects of distal mutations were reviewed [36] , [86] and studied in a number of research articles [34] , [35] .…”