State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Medicinal Chemistry and Bioinformatics Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Nucleic Acids Res. 2024 Jan 5;52(D1):D376-D383. doi: 10.1093/nar/gkad915.
Allosteric regulation, induced by perturbations at an allosteric site topographically distinct from the orthosteric site, is one of the most direct and efficient ways to fine-tune macromolecular function. The Allosteric Database (ASD; accessible online at http://mdl.shsmu.edu.cn/ASD) has been systematically developed since 2009 to provide comprehensive information on allosteric regulation. In recent years, allostery has seen sustained growth and wide-ranging applications in life sciences, from basic research to new therapeutics development, while also elucidating emerging obstacles across allosteric research stages. To overcome these challenges and maintain high-quality data center services, novel features were curated in the ASD2023 update: (i) 66 589 potential allosteric sites, covering > 80% of the human proteome and constituting the human allosteric pocketome; (ii) 748 allosteric protein-protein interaction (PPI) modulators with clear mechanisms, aiding protein machine studies and PPI-targeted drug discovery; (iii) 'Allosteric Hit-to-Lead,' a pioneering dataset providing panoramic views from 87 well-defined allosteric hits to 6565 leads and (iv) 456 dualsteric modulators for exploring the simultaneous regulation of allosteric and orthosteric sites. Meanwhile, ASD2023 maintains a significant growth of foundational allosteric data. Based on these efforts, the allosteric knowledgebase is progressively evolving towards an integrated landscape, facilitating advancements in allosteric target identification, mechanistic exploration and drug discovery.
变构调节是通过变构位点的扰动来实现的，与正构位点在拓扑上不同，是精细调节生物大分子功能的最直接和有效的方法之一。变构数据库（ASD；可在 http://mdl.shsmu.edu.cn/ASD 在线访问）自 2009 年以来一直在系统地开发，以提供有关变构调节的综合信息。近年来，变构作用在生命科学领域得到了持续的发展和广泛的应用，从基础研究到新疗法的开发，同时也阐明了变构研究各个阶段出现的新障碍。为了克服这些挑战并保持高质量的数据中心服务，在 ASD2023 更新中精心策划了新的功能：（i）66589 个潜在的变构位点，覆盖了>80%的人类蛋白质组，构成了人类变构口袋组；（ii）748 种具有明确机制的变构蛋白-蛋白相互作用（PPI）调节剂，有助于蛋白质机器研究和 PPI 靶向药物发现；（iii）“变构命中先导物”，这是一个开创性的数据集，提供了 87 种明确的变构命中物到 6565 种先导物的全景视图；（iv）456 种双变构调节剂，用于探索变构和正构位点的同时调节。同时，ASD2023 保持了基础变构数据的显著增长。基于这些努力，变构知识库正在逐步向一个综合的景观发展，促进变构靶标识别、机制探索和药物发现的进展。
