figshare
Browse

Proteome-wide identification and comparison of drug pockets for discovering new drug indications and side effects

Download all (13.46 GB)
Version 8 2025-01-11, 06:46
Version 7 2024-12-31, 13:19
Version 6 2024-12-31, 09:18
Version 5 2024-12-31, 08:43
Version 4 2024-12-30, 02:12
Version 3 2024-12-29, 12:11
Version 2 2024-12-23, 09:23
Version 1 2024-11-23, 09:51
dataset
posted on 2025-01-11, 06:46 authored by Renxin ZhangRenxin Zhang

Drug development faces significant financial and time challenges, highlighting the need for more efficient strategies. This study evaluated the druggability of the entire human proteome using Fpocket. We identified 15,043 druggable pockets in 20,255 predicted protein structures, significantly expanding the estimated druggable proteome from 3,000 to over 11,000 proteins. Notably, many druggable pockets were found in less-studied proteins, suggesting untapped therapeutic opportunities. Pairwise pocket similarity analysis identified 220,312 similar pocket pairs, with 3,241 pairs across different protein families, indicating shared drug-binding potential. In addition, 62,077 significant matches were found between druggable pockets and 1,872 known drug pockets, highlighting candidates for drug repositioning. We repositioned progesterone to ADGRD1 for pemphigus and breast cancer, and estradiol to ANO2 for shingles and medulloblastoma, which were validated by molecular docking. To assess safety, off-target effects were analyzed for the drugs such as axitinib, linking newly identified targets with known side effects. For axitinib, 127 new targets were identified and 46 out of 48 documented side effects were linked to these targets. These findings demonstrate the utility of pocket similarity in drug repositioning, target expansion, and improved drug safety evaluation, offering new avenues for the discovery of new indications and side effects of existing drugs.

Funding

National Natural Science Foundation of China (32160153 and 32300551)

Yunnan Fundamental Research Projects (202105AD160008 and 202102AA100053)

“Xingdian Talent Support Program” of Yunnan Province (KKXY202473008)

Science Foundation of Department of Education of Yunnan Province (No. 2023J041)

History

Usage metrics

    Categories

    Keywords

    druggabilityproteomedrug repurposingside effects predictiondrug-protein interactions

    Licence

    CC BY 4.0

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC