ArticleBiopolymers2008
A poke in the eye: inhibiting HIV-1 protease through its flap-recognition pocket.
Article in Biopolymers, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed.
- Subtype-Specific HIV-1 Protease and the Role of Hinge and Flap Dynamics in Drug Resistance: A Subtype C Narrative.Viruses · 2025Review
- Elasticity-Associated Functionality and Inhibition of the HIV Protease.Advances in experimental medicine and biology · 2022Article
- Molecular Docking-Based Screening for Novel Inhibitors of the Human Immunodeficiency Virus Type 1 Protease that Effectively Reduce the Viral Replication in Human Cells.Journal of AIDS & clinical research · 2021Article
- Driving Structure-Based Drug Discovery through Cosolvent Molecular Dynamics.Journal of medicinal chemistry · 2016Review
- Identifying binding hot spots on protein surfaces by mixed-solvent molecular dynamics: HIV-1 protease as a test case.Biopolymers · 2016Article
- Parameter choice matters: validating probe parameters for use in mixed-solvent simulations.Journal of chemical information and modeling · 2014Article
- An allosteric modulator of HIV-1 protease shows equipotent inhibition of wild-type and drug-resistant proteases.Journal of medicinal chemistry · 2014Article
- Protein flexibility in docking and surface mapping.Quarterly reviews of biophysics · 2012Review
- Text mining improves prediction of protein functional sites.PloS one · 2012Article
- Binding to the open conformation of HIV-1 protease.Proteins · 2011Article
- Insights into the dynamics of HIV-1 protease: a kinetic network model constructed from atomistic simulations.Journal of the American Chemical Society · 2011Article
- Article
- Full protein flexibility is essential for proper hot-spot mapping.Journal of the American Chemical Society · 2011Article
- Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters.The FEBS journal · 2010Article
- Identification of broad-based HIV-1 protease inhibitors from combinatorial libraries.The Biochemical journal · 2010Article
- Fragment-based screen against HIV protease.Chemical biology & drug design · 2010Article
- Modulation of catalytic function by differential plasticity of the active site: case study of Trypanosoma cruzi trans-sialidase and Trypanosoma rangeli sialidase.Biochemistry · 2009Article
- Clarifying allosteric control of flap conformations in the 1TW7 crystal structure of HIV-1 protease.Proteins · 2009Article
- Mutational analysis and allosteric effects in the HIV-1 capsid protein carboxyl-terminal dimerization domain.Biomacromolecules · 2009Article
- Automated clustering of probe molecules from solvent mapping of protein surfaces: new algorithms applied to hot-spot mapping and structure-based drug design.Journal of computer-aided molecular design · 2008Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
A novel mechanism of inhibiting HIV-1 protease (HIVp) is presented. Using computational solvent mapping to identify complementary interactions and the Multiple Protein Structure method to incorporate protein flexibility, we generated a receptor-based pharmacophore model of the flexible flap region of the semiopen, apo state of HIVp. Complementary interactions were consistently observed at the base of the flap, only within a cleft with a specific structural role. In the closed, bound state of HIVp, each flap tip docks against the opposite monomer, occupying this cleft. This flap-recognition site is filled by the protein and cannot be identified using traditional approaches based on bound, closed structures. Virtual screening and dynamics simulations show how small molecules can be identified to complement this cleft. Subsequent experimental testing confirms inhibitory activity of this new class of inhibitor. This may be the first new inhibitor class for HIVp since dimerization inhibitors were introduced 17 years ago.
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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.