ArticleScientific reports2019
Modulation of Human Hsp90α Conformational Dynamics by Allosteric Ligand Interaction at the C-Terminal Domain.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- In-Depth Molecular Dynamics Simulations Reveal Ligand-Induced Modulations of the HSPA8-SARS-CoV-2 Spike Protein Interaction.International journal of molecular sciences · 2026Article
- Investigation of a cryptic ligand binding site on Plasmodium falciparum Hsp90.Bioorganic & medicinal chemistry · 2025Article
- Impact of African-Specific ACE2 Polymorphisms on Omicron BA.4/5 RBD Binding and Allosteric Communication Within the ACE2-RBD Protein Complex.International journal of molecular sciences · 2025Article
- Allosteric modulation of Plasmodium falciparum Isoleucyl tRNA synthetase by South African natural compounds.PloS one · 2025Article
- Corilagin ameliorates macrophages inflammation in atherosclerosis through TLR4-NFκB/MAPK pathway.Heliyon · 2023Article
- Crystal structure of the middle and C-terminal domains of Hsp90α labeled with a coumarin derivative reveals a potential allosteric binding site as a drug target.Acta crystallographica. Section D, Structural biology · 2022Article
- Deciphering Isoniazid Drug Resistance Mechanisms on DimericACS omega · 2022Article
- Evolutionary progression of collective mutations in Omicron sub-lineages towards efficient RBD-hACE2: Allosteric communications between and within viral and human proteins.Computational and structural biotechnology journal · 2022Article
- Computational Applications in Secondary Metabolite Discovery (CAiSMD): an online workshop.Journal of cheminformatics · 2021Article
- Using NMR to identify binding regions for N and C-terminal Hsp90 inhibitors using Hsp90 domains.RSC medicinal chemistry · 2021Article
- Decoding the Molecular Effects of Atovaquone Linked Resistant Mutations onInternational journal of molecular sciences · 2021Article
- Allosteric pockets and dynamic residue network hubs of falcipain 2 in mutations including those linked to artemisinin resistance.Computational and structural biotechnology journal · 2021Article
- MDM-TASK-web: MD-TASK and MODE-TASK web server for analyzing protein dynamics.Computational and structural biotechnology journal · 2021Article
- Novel dynamic residue network analysis approaches to study allosteric modulation: SARS-CoV-2 MComputational and structural biotechnology journal · 2021Article
- Understanding the Pyrimethamine Drug Resistance Mechanism via Combined Molecular Dynamics and Dynamic Residue Network Analysis.Molecules (Basel, Switzerland) · 2020Article
- Integrated Computational Approaches and Tools forAllosteric Drug Discovery.International journal of molecular sciences · 2020Review
- Determining the unbinding events and conserved motions associated with the pyrazinamide release due to resistance mutations ofComputational and structural biotechnology journal · 2020Article
- Establishing Computational Approaches Towards Identifying Malarial Allosteric Modulators: A Case Study ofInternational journal of molecular sciences · 2019Article
- South African Abietane Diterpenoids and Their Analogs as Potential Antimalarials: Novel Insights from Hybrid Computational Approaches.Molecules (Basel, Switzerland) · 2019Article
- Mechanism of Action of Non-Synonymous Single Nucleotide Variations Associated withMolecules (Basel, Switzerland) · 2019Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent years have seen heat shock protein 90 kDa (Hsp90) attract significant interest as a viable drug target, particularly for cancer. To date, designed inhibitors that target the ATPase domain demonstrate potent anti-proliferative effects, but have failed clinical trials due to high levels of associated toxicity. To circumvent this, the focus has shifted away from the ATPase domain. One option involves modulation of the protein through allosteric activation/inhibition. Here, we propose a novel approach: we use previously obtained information via residue perturbation scanning coupled with dynamic residue network analysis to identify allosteric drug targeting sites for inhibitor docking. We probe the open conformation of human Hsp90α for druggable sites that overlap with these allosteric control elements, and identify three putative natural compound allosteric modulators: Cephalostatin 17, 20(29)-Lupene-3β-isoferulate and 3'-Bromorubrolide F. We assess the allosteric potential of these ligands by examining their effect on the conformational dynamics of the protein. We find evidence for the selective allosteric activation and inhibition of Hsp90's conformational transition toward the closed state in response to ligand binding and shed valuable insight to further the understanding of allosteric drug design and Hsp90's complex allosteric mechanism of action.
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