ArticleJournal of the American Chemical Society2010
Toward flexibility-activity relationships by NMR spectroscopy: dynamics of Pin1 ligands.
Article in Journal of the American Chemical Society, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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.
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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
28 citing papers in PubMed, 55 citations in OpenAlex.
- Pin1 WW Domain Ligand Library Synthesized with an Easy Solid-Phase Phosphorylating Reagent.Biochemistry · 2024Article
- Understanding and Quantifying Molecular Flexibility: Torsion Angular Bin Strings.Journal of chemical information and modeling · 2024Article
- Ligand-specific conformational change drives interdomain allostery in Pin1.Nature communications · 2022Article
- The role of NMR in leveraging dynamics and entropy in drug design.Journal of biomolecular NMR · 2020Article
- NMR Relaxation Dispersion Reveals Macrocycle Breathing Dynamics in a Cyclodextrin-based Rotaxane.Journal of the American Chemical Society · 2020Article
- Spotlight on the Ballet of Proteins: The Structural Dynamic Properties of Proteins Illuminated by Solution NMR.International journal of molecular sciences · 2020Review
- Activity and Affinity of Pin1 Variants.Molecules (Basel, Switzerland) · 2019Review
- Molecular Mechanism of the Pin1-Histone H1 Interaction.Biochemistry · 2019Article
- Label-free NMR-based dissociation kinetics determination.Journal of biomolecular NMR · 2017Article
- Enzyme Selectivity Fine-Tuned through Dynamic Control of a Loop.Angewandte Chemie (International ed. in English) · 2016Article
- Allosteric Communication across STAT3 Domains Associated with STAT3 Function and Disease-Causing Mutation.Journal of molecular biology · 2016Article
- Chemical Tools To Decipher Regulation of Phosphatases by Proline Isomerization on Eukaryotic RNA Polymerase II.ACS chemical biology · 2015Article
- Investigating Dynamic Interdomain Allostery in Pin1.Biophysical reviews · 2015Article
- Enzyme dynamics from NMR spectroscopy.Accounts of chemical research · 2015Review
- Ligand-detected relaxation dispersion NMR spectroscopy: dynamics of preQ1-RNA binding.Angewandte Chemie (International ed. in English) · 2015Article
- Stereochemical Control in the Still-Wittig Rearrangement Synthesis of Cyclohexyl (Z)-Alkene Inhibitors of Pin1.PloS one · 2015Article
- Interdomain interactions support interdomain communication in human Pin1.Biochemistry · 2013Article
- A prolyl-isomerase mediates dopamine-dependent plasticity and cocaine motor sensitization.Cell · 2013Article
- Structural and kinetic analysis of prolyl-isomerization/phosphorylation cross-talk in the CTD code.ACS chemical biology · 2012Article
- Exposing the Moving Parts of Proteins with NMR Spectroscopy.The journal of physical chemistry letters · 2012Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Drug design involves iterative ligand modifications. For flexible ligands, these modifications often entail restricting conformational flexibility. However, defining optimal restriction strategies can be challenging if the relationship between ligand flexibility and biological activity is unclear. Here, we describe an approach for ligand flexibility-activity studies using Nuclear Magnetic Resonance (NMR) spin relaxation. Specifically, we use (13)C relaxation dispersion measurements to compare site-specific changes in ligand flexibility for a series of related ligands that bind a common macromolecular receptor. The flexibility changes reflect conformational reorganization resulting from formation of the receptor-ligand complex. We demonstrate this approach on three structurally similar but flexibly differentiated ligands of human Pin1, a peptidyl-prolyl isomerase. The approach is able to map the ligand dynamics relevant for activity and expose changes in those dynamics caused by conformational locking. Thus, NMR flexibility-activity studies can provide information to guide strategic ligand rigidification. As such, they help establish an experimental basis for developing flexibility-activity relationships (FAR) to complement traditional structure-activity relationships (SAR) in molecular design.
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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.