ArticleACS omega2018
Conformational Sampling of Macrocyclic Drugs in Different Environments: Can We Find the Relevant Conformations?
Article in ACS omega, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
35 citing papers in PubMed, 89 citations in OpenAlex.
- What Is in a Structure? Cell Permeability and Solubility of Series of Macrocycles and Linear Matched Pairs.Journal of medicinal chemistry · 2026Article
- Article
- Conformational Trajectory of the Molecular Chameleon Grazoprevir From Formulation to Target-Bound.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Flexible molecular chameleons: structural adaptability and therapeutic applications.Frontiers in chemistry · 2026Review
- Rational Activity Improvement of Cyclic Peptides through Stabilization and Rigidification of Main Chain Using φ/ψ Plots of Amino Acids.ACS omega · 2025Article
- Molecular chameleons in drug discovery.Nature reviews. Chemistry · 2024Review
- Addressing Challenges of Macrocyclic Conformational Sampling in Polar and Apolar Solvents: Lessons for Chameleonicity.Journal of chemical information and modeling · 2023Article
- High-Quality Conformer Generation with CONFORGE: Algorithm and Performance Assessment.Journal of chemical information and modeling · 2023Article
- Chamelogk: A Chromatographic Chameleonicity Quantifier to Design Orally Bioavailable Beyond-Rule-of-5 Drugs.Journal of medicinal chemistry · 2023Article
- Macrocycles in Drug Discovery─Learning from the Past for the Future.Journal of medicinal chemistry · 2023Review
- Conformational Sampling Deciphers the Chameleonic Properties of a VHL-Based Degrader.Pharmaceutics · 2023Article
- Simulation Reveals the Chameleonic Behavior of Macrocycles.Journal of chemical information and modeling · 2023Article
- Linker-Dependent Folding Rationalizes PROTAC Cell Permeability.Journal of medicinal chemistry · 2022Article
- Refinement of Computational Access to Molecular Physicochemical Properties: From Ro5 to bRo5.Journal of medicinal chemistry · 2022Article
- Pushing the Limits of Characterising a Weak Halogen Bond in Solution.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Structure prediction of cyclic peptides by molecular dynamics + machine learning.Chemical science · 2021Article
- Managing Experimental 3D Structures in the Beyond-Rule-of-5 Chemical Space: The Case of Rifampicin.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Prediction of n-octanol/water partition coefficients and acidity constants (pKJournal of computer-aided molecular design · 2021Article
- Cell Permeability of Isomeric Macrocycles: Predictions and NMR Studies.ACS medicinal chemistry letters · 2021Article
- Solution-State Preorganization of Cyclic β-Hairpin Ligands Determines Binding Mechanism and Affinities for MDM2.Journal of chemical information and modeling · 2021Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Conformational flexibility is a major determinant of the properties of macrocycles and other drugs in beyond rule of 5 (bRo5) space. Prediction of conformations is essential for design of drugs in this space, and we have evaluated three tools for conformational sampling of a set of 10 bRo5 drugs and clinical candidates in polar and apolar environments. The distance-geometry based OMEGA was found to yield ensembles spanning larger structure and property spaces than the ensembles obtained by MOE-LowModeMD (MOE) and MacroModel (MC). Both MC and OMEGA but not MOE generated different ensembles for polar and apolar environments. All three conformational search methods generated conformers similar to the crystal structure conformers for 9 of the 10 compounds, with OMEGA performing somewhat better than MOE and MC. MOE and OMEGA found all six conformers of roxithromycin that were identified by NMR in aqueous solutions, whereas only OMEGA sampled the three conformers observed in chloroform. We suggest that characterization of conformers using molecular descriptors, e.g., the radius of gyration and polar surface area, is preferred to energy- or root-mean-square deviation-based methods for selection of biologically relevant conformers in drug discovery in bRo5 space.
Identifiers
What OpenQuestion holds
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.