ArticleBiophysical chemistry2014
Statistical allosteric coupling to the active site indole ring flip equilibria in the FK506-binding domain.
Article in Biophysical chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 6 citations in OpenAlex.
- An overview of recent molecular dynamics applications as medicinal chemistry tools for the undruggable site challenge.MedChemComm · 2018Review
- Coupling of Conformational Transitions in the N-terminal Domain of the 51-kDa FK506-binding Protein (FKBP51) Near Its Site of Interaction with the Steroid Receptor Proteins.The Journal of biological chemistry · 2015Article
- Conformational Dynamics in FKBP Domains: Relevance to Molecular Signaling and Drug Design.Current molecular pharmacology · 2015Review
- Molecular dynamics simulations: advances and applications.Advances and applications in bioinformatics and chemistry : AABC · 2015Review
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Authors and funding
4 authors at 4 institutions in 1 country.
Funding
Abstract
In solution, the Trp 59 indole ring at the base of the active site cleft in the FKBP domain protein FKBP12 is rotated by ~90° at a population level of 20%, relative to its canonical crystallographic orientation. NMR measurements on the homologous FK1 domains of human FKBP51 and FKBP52 indicate no observable indole ring flip conformation, while the V101I variant of FKBP12 decreases the population having a perpendicular indole orientation by 10-fold. A set of three parallel 400 ns CHARMM27 molecular simulations for both wild type FKBP12 and the V101I variant examined how this ring flip might be energetically coupled to a transition of the Glu 60 sidechain which interacts with the backbone of the 50's loop located ~12 Å from the indole nitrogen. Analysis of the transition matrix for the local dynamics of the Glu 60 sidechain, the Trp 59 sidechain, and of the structurally interposed α-helix hydrogen bonding pattern yielded a statistical allosteric coupling of 10 kJ/mol with negligible concerted dynamical coupling for the transitions of the two sidechains.
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