ArticleBioinformatics advances2023
Investigating the conformational landscape of AlphaFold2-predicted protein kinase structures.
Article in Bioinformatics advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Multiple disulfide-bonded states confer extensive conformational diversity in fibrinogen.Protein science : a publication of the Protein Society · 2026Article
- Fine-Tuning DiffDock-L for Allosteric Kinase Docking.Journal of chemical information and modeling · 2026Article
- Conformational dynamics in insulin receptor kinase reveal a type III allosteric pocket.Protein science : a publication of the Protein Society · 2026Article
- Learnable protein representations in computational biology for predicting drug-target affinity.Journal of cheminformatics · 2026Review
- Can Deep Learning Blind Docking Methods be Used to Predict Allosteric Compounds?Journal of chemical information and modeling · 2025Article
- Probing Functional Allosteric States and Conformational Ensembles of the Allosteric Protein Kinase States and Mutants: Atomistic Modeling and Comparative Analysis of AlphaFold2, OmegaFold, and AlphaFlow Approaches and Adaptations.The journal of physical chemistry. B · 2024Article
- Exploring the conformational landscape of protein kinases.Current opinion in structural biology · 2024Review
- Empowering AlphaFold2 for protein conformation selective drug discovery with AlphaFold2-RAVE.eLife · 2024Article
- Empowering AlphaFold2 for protein conformation selective drug discovery with AlphaFold2-RAVE.ArXiv · 2024Article
- A comprehensive exploration of the druggable conformational space of protein kinases using AI-predicted structures.PLoS computational biology · 2024Article
- Efficient Refinement of Complex Structures of Flexible Histone Peptides Using Post-Docking Molecular Dynamics Protocols.International journal of molecular sciences · 2024Article
- AlphaFold2 captures the conformational landscape of the HAMP signaling domain.Protein science : a publication of the Protein Society · 2024Article
- AlphaFold2 in biomedical research: facilitating the development of diagnostic strategies for disease.Frontiers in molecular biosciences · 2024Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Summary: Protein kinases are a family of signaling proteins, crucial for maintaining cellular homeostasis. When dysregulated, kinases drive the pathogenesis of several diseases, and are thus one of the largest target categories for drug discovery. Kinase activity is tightly controlled by switching through several active and inactive conformations in their catalytic domain. Kinase inhibitors have been designed to engage kinases in specific conformational states, where each conformation presents a unique physico-chemical environment for therapeutic intervention. Thus, modeling kinases across conformations can enable the design of novel and optimally selective kinase drugs. Due to the recent success of AlphaFold2 in accurately predicting the 3D structure of proteins based on sequence, we investigated the conformational landscape of protein kinases as modeled by AlphaFold2. We observed that AlphaFold2 is able to model several kinase conformations across the kinome, however, certain conformations are only observed in specific kinase families. Furthermore, we show that the per residue predicted local distance difference test can capture information describing structural flexibility of kinases. Finally, we evaluated the docking performance of AlphaFold2 kinase structures for enriching known ligands. Taken together, we see an opportunity to leverage AlphaFold2 models for structure-based drug discovery against kinases across several pharmacologically relevant conformational states. Availability and implementation: All code used in the analysis is freely available at https://github.com/Harmonic-Discovery/AF2-kinase-conformational-landscape.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.