ASD2023: towards the integrating landscapes of allosteric knowledgebase.

Journal: Nucleic acids research
PMID: 37870448

Abstract

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.

Authors

  • Jixiao He
    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.
  • Xinyi Liu
    Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha 410011, China.
  • Chunhao Zhu
    College of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia 750004, China.
  • Jinyin Zha
    Medicinal Chemistry and Bioinformatics Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • Qian Li
    Emergency and Critical Care Center, Department of Emergency Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China.
  • Mingzhu Zhao
    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.
  • Jiacheng Wei
    Medicinal Chemistry and Bioinformatics Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • Mingyu Li
    College of Pharmacy, Ningxia Medical University, Yinchuan, NingxiaHui Autonomous Region, China.
  • Chengwei Wu
    State Key Laboratory of Structure Analysis for Industrial Equipment, Department of Engineering Mechanics, Dalian University of Technology, Dalian, 116024, China.
  • Junyuan Wang
    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.
  • Yonglai Jiao
    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.
  • Shaobo Ning
    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.
  • Jiamin Zhou
    Department of Radiology and Biomedical Imaging, School of Medicine, University of California, San Francisco, San Francisco, CA, United States.
  • Yue Hong
    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.
  • Yonghui Liu
    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.
  • Hongxi He
    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.
  • Mingyang Zhang
    School of Quality and Technical Supervision, Hebei University, Baoding, Hebei 071002, P.R.China.
  • Feiying Chen
    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.
  • Yanxiu Li
    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.
  • Xinheng He
    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.
  • Jing Wu
    School of Pharmaceutical Science, Jiangnan University, Wuxi, 214122, Jiangsu, China.
  • Shaoyong Lu
    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.
  • Kun Song
    Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, 250012, China.
  • Xuefeng Lu
    Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
  • Jian Zhang
    College of Pharmacy, Ningxia Medical University, Yinchuan, NingxiaHui Autonomous Region, China.

Keywords

External Resources

Popular Topics
Recent Journals