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PreprintCited by 14Computational Drug Discovery MethodsProtein Interaction Studies and Fluorescence AnalysisProtein Structure and Dynamics

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Benchmarking Reverse Docking through AlphaFold2 Human Proteome

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Luo, Qing, Wang, Sheng, Li, Hoi Yeung, Zheng, Liangzhen, Mu, Yuguang, Guo, Jingjing·2023·Protein Science
DOI 10.1101/2023.12.16.572027PMC PMC11400627

Preprint — published as 10.1002/pro.5167

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Abstract

Predicting binding of a small molecule to the human proteome by reverse docking methods, we can predict the target interactions of drug compounds in the human body, as well as further evaluate their potential off-target effects or toxic side effects. In this study, we constructed 11 pipelines to evaluate and benchmark thoroughly the predictive capabilities of these reverse docking pipelines. The pipelines were built using site prediction tools (PointSite and SiteMap) based on the AF2 human proteome, docking programs (Glide and AutoDock Vina), and scoring functions (Glide, Autodock Vina, RTMScore, DeepRMSD, OnionNet-SFCT). The results show that pipeline glide_sfct (PS) exhibited the best target prediction ability and successfully predicted the similar proteins of native targets. This finding provides important clues for understanding the promiscuity between the drug ligand and the whole human proteome. In general, our study has the potential to increase the success rate and reduce the development timeline of drug discovery, thereby saving costs.

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Metadata

Authors
Luo, Q., Wang, S., Li, H. Y., Zheng, L., Mu, Y., & Guo, J.
Affiliations
  • Macao Polytechnic University (MO)
  • Shenzhen YHLO Biotech Co., Ltd. (China) (CN)
  • Chinese Academy of Sciences (CN)
  • Nanyang Technological University (SG)
Corresponding author
  • Zheng, Liangzhen
  • Mu, Yuguang
  • Guo, Jingjing
ORCID
Venue
Protein Science
Publisher
openRxiv
Published
2023-12-17
Volume
33
Issue
10
Pages
e5167-e5167
ISSN
0961-8368 (ISSN-L)
DOI
10.1101/2023.12.16.572027
PMC
PMC11400627
OpenAlex
W4402534001
Cited by
14
References
1
Citations by year
2026: 4 · 2025: 8 · 2024: 2
FWCI
2.96
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Protein Science (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion)
  • DR-NTU (Nanyang Technological University) (submittedVersion)
Funders
  • Ministry of Education, India
  • Zhejiang University
  • ShanghaiTech University
  • National Key Research and Development Program of China (2023YFA0915500)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
reverse docking, drug target prediction, site map, glides, AutoDock Vina, off-target effects, drug repurposing, toxicity prediction
MeSH terms
Humans, Ligands, Protein Binding, Protein Conformation, Software, Benchmarking, Proteome, Molecular Docking Simulation

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