ArticleChemical science2020
Dynamic design: manipulation of millisecond timescale motions on the energy landscape of cyclophilin A.
Article in Chemical science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 32 citations in OpenAlex.
- RelCalc: symbolic evaluation of BWR theory relaxation rates in python, applications to TROSY effects in AX[Formula: see text] spin systems.Journal of biomolecular NMR · 2026Article
- Molecular driving force of a small molecule-induced protein disorder-order transition.Communications chemistry · 2026Article
- Markovian state models uncover casein kinase 1 dynamics that govern circadian period.Biophysical journal · 2025Article
- Investigating the binding mechanism of AML inhibitors based on panobinostat with HDAC3 proteins using Gaussian accelerated molecular dynamics.RSC advances · 2025Article
- Comparison of Methodologies for Absolute Binding Free Energy Calculations of Ligands to Intrinsically Disordered Proteins.Journal of chemical theory and computation · 2024Article
- Interactions between Inhibitors and 5-Lipoxygenase: Insights from Gaussian Accelerated Molecular Dynamics and Markov State Models.International journal of molecular sciences · 2024Article
- Markov State Models: To Optimize or Not to Optimize.Journal of chemical theory and computation · 2024Article
- Binding of Cholesterol to the N-Terminal Domain of the NPC1L1 Transporter: Analysis of the Epimerization-Related Binding Selectivity and Loop Mutations.Journal of chemical information and modeling · 2024Article
- Protein conformational ensembles in function: roles and mechanisms.RSC chemical biology · 2023Review
- Deconstructing allostery by computational assessment of the binding determinants of allosteric PTP1B modulators.Communications chemistry · 2023Article
- Anisotropic Electrostatic Interactions in Coarse-Grained Water Models to Enhance the Accuracy and Speed-Up Factor of Mesoscopic Simulations.The journal of physical chemistry. B · 2021Article
- Discovery of a hidden transient state in all bromodomain families.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Markov state models and NMR uncover an overlooked allosteric loop in p53.Chemical science · 2020Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteins need to interconvert between many conformations in order to function, many of which are formed transiently, and sparsely populated. Particularly when the lifetimes of these states approach the millisecond timescale, identifying the relevant structures and the mechanism by which they interconvert remains a tremendous challenge. Here we introduce a novel combination of accelerated MD (aMD) simulations and Markov state modelling (MSM) to explore these 'excited' conformational states. Applying this to the highly dynamic protein CypA, a protein involved in immune response and associated with HIV infection, we identify five principally populated conformational states and the atomistic mechanism by which they interconvert. A rational design strategy predicted that the mutant D66A should stabilise the minor conformations and substantially alter the dynamics, whereas the similar mutant H70A should leave the landscape broadly unchanged. These predictions are confirmed using CPMG and R
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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.