ArticleProceedings of the National Academy of Sciences of the United States of America2015
Homologous ligands accommodated by discrete conformations of a buried cavity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 54 citations in OpenAlex.
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- Kinetics-Based State Definitions for Discrete Binding Conformations of T4 L99A in MD via Markov State Modeling.Journal of chemical information and modeling · 2024Article
- PopShift: A Thermodynamically Sound Approach to Estimate Binding Free Energies by Accounting for Ligand-Induced Population Shifts from a Ligand-Free Markov State Model.Journal of chemical theory and computation · 2024Article
- Pan-HSP90 ligand binding reveals isoform-specific differences in plasticity and water networks.Protein science : a publication of the Protein Society · 2023Article
- Accelerated Enveloping Distribution Sampling (AEDS) Allows for Efficient Sampling of Orthogonal Degrees of Freedom.Journal of chemical information and modeling · 2023Article
- Large-Scale Ligand Perturbations of the Protein Conformational Landscape Reveal State-Specific Interaction Hotspots.Journal of medicinal chemistry · 2022Article
- Flexible CDOCKER: Hybrid Searching Algorithm and Scoring Function with Side Chain Conformational Entropy.Journal of chemical information and modeling · 2021Article
- Energy penalties enhance flexible receptor docking in a model cavity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Temperature artifacts in protein structures bias ligand-binding predictions.Chemical science · 2021Article
- Accurate absolute free energies for ligand-protein binding based on non-equilibrium approaches.Communications chemistry · 2021Article
- Property-Unmatched Decoys in Docking Benchmarks.Journal of chemical information and modeling · 2021Article
- A Geometric Definition of Short to Medium Range Hydrogen-Mediated Interactions in Proteins.Molecules (Basel, Switzerland) · 2020Article
- Protein-ligand binding with the coarse-grained Martini model.Nature communications · 2020Article
- De Novo Prediction of Binders and Nonbinders for T4 Lysozyme by gREST Simulations.Journal of chemical information and modeling · 2019Article
- Exploring the strength of a hydrogen bond as a function of steric environment using 1,2-azaborine ligands and engineered T4 lysozyme receptors.Organic & biomolecular chemistry · 2019Article
- Enhancing Side Chain Rotamer Sampling Using Nonequilibrium Candidate Monte Carlo.Journal of chemical theory and computation · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Conformational change in protein-ligand complexes is widely modeled, but the protein accommodation expected on binding a congeneric series of ligands has received less attention. Given their use in medicinal chemistry, there are surprisingly few substantial series of congeneric ligand complexes in the Protein Data Bank (PDB). Here we determine the structures of eight alkyl benzenes, in single-methylene increases from benzene to n-hexylbenzene, bound to an enclosed cavity in T4 lysozyme. The volume of the apo cavity suffices to accommodate benzene but, even with toluene, larger cavity conformations become observable in the electron density, and over the series two other major conformations are observed. These involve discrete changes in main-chain conformation, expanding the site; few continuous changes in the site are observed. In most structures, two discrete protein conformations are observed simultaneously, and energetic considerations suggest that these conformations are low in energy relative to the ground state. An analysis of 121 lysozyme cavity structures in the PDB finds that these three conformations dominate the previously determined structures, largely modeled in a single conformation. An investigation of the few congeneric series in the PDB suggests that discrete changes are common adaptations to a series of growing ligands. The discrete, but relatively few, conformational states observed here, and their energetic accessibility, may have implications for anticipating protein conformational change in ligand design.
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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.