ArticleProceedings of the National Academy of Sciences of the United States of America2016
Elucidating the druggable interface of protein-protein interactions using fragment docking and coevolutionary analysis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
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- Natural Product Synthesis in the 21st Century: Beyond the Mountain Top.ACS central science · 2024Review
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- An in silico investigation on the binding site preference of PD-1 and PD-L1 for designing antibodies for targeted cancer therapy.PloS one · 2024Article
- Engineering gain-of-function mutants of a WW domain by dynamics and structural analysis.Protein science : a publication of the Protein Society · 2023Article
- Artificial Intelligence and Machine Learning Technology Driven Modern Drug Discovery and Development.International journal of molecular sciences · 2023Review
- Integrating Protein Interaction Surface Prediction with a Fragment-Based Drug Design: Automatic Design of New Leads with Fragments on Energy Surfaces.Journal of chemical information and modeling · 2023Article
- FragDPI: a novel drug-protein interaction prediction model based on fragment understanding and unified coding.Frontiers of computer science · 2023Article
- Coupling a Live Cell Directed Evolution Assay with Coevolutionary Landscapes to Engineer an Improved Fluorescent Rhodopsin Chloride Sensor.ACS synthetic biology · 2022Article
- Discovery of potential small molecular SARS-CoV-2 entry blockers targeting the spike protein.Acta pharmacologica Sinica · 2022Article
- A VDAC1-mediated NEET protein chain transfers [2Fe-2S] clusters between the mitochondria and the cytosol and impacts mitochondrial dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Machine Learning in Drug Discovery: A Review.Artificial intelligence review · 2022Article
- CKB inhibits epithelial-mesenchymal transition and prostate cancer progression by sequestering and inhibiting AKT activation.Neoplasia (New York, N.Y.) · 2021Article
- Identifying hydrophobic protein patches to inform protein interaction interfaces.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Geometrical and electro-static determinants of protein-protein interactions.Bioinformation · 2021Article
- Combined Protein- and Ligand-Observed NMR Workflow to Screen Fragment Cocktails against Multiple Proteins: A Case Study Using Bromodomains.Molecules (Basel, Switzerland) · 2020Article
- A Practical Perspective on the Roles of Solution NMR Spectroscopy in Drug Discovery.Molecules (Basel, Switzerland) · 2020Review
- Epistatic contributions promote the unification of incompatible models of neutral molecular evolution.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
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5 authors.
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Abstract
Protein-protein interactions play a central role in cellular function. Improving the understanding of complex formation has many practical applications, including the rational design of new therapeutic agents and the mechanisms governing signal transduction networks. The generally large, flat, and relatively featureless binding sites of protein complexes pose many challenges for drug design. Fragment docking and direct coupling analysis are used in an integrated computational method to estimate druggable protein-protein interfaces. (i) This method explores the binding of fragment-sized molecular probes on the protein surface using a molecular docking-based screen. (ii) The energetically favorable binding sites of the probes, called hot spots, are spatially clustered to map out candidate binding sites on the protein surface. (iii) A coevolution-based interface interaction score is used to discriminate between different candidate binding sites, yielding potential interfacial targets for therapeutic drug design. This approach is validated for important, well-studied disease-related proteins with known pharmaceutical targets, and also identifies targets that have yet to be studied. Moreover, therapeutic agents are proposed by chemically connecting the fragments that are strongly bound to the hot spots.
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