Abstract
Steered molecular dynamics simulations of ligand dissociation from Thyroid hormone receptors indicate that dissociation is favored via rearrangements in a mobile part of the LBD comprising H3, the loop between H1 and H2, and nearby beta-sheets, contrary to current models in which the H12 is mostly involved. Dissociation is facilitated in this path by the interaction of the hydrophilic part of the ligand with external water molecules, suggesting strategies to enhance ligand binding affinity.
Keywords
ChemistryDissociation (chemistry)ReceptorLigand (biochemistry)ThyroidHormoneStereochemistryEndocrinologyBiochemistryPhysical chemistry
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Publication Info
- Year
- 2005
- Type
- article
- Volume
- 49
- Issue
- 1
- Pages
- 23-26
- Citations
- 83
- Access
- Closed
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Cite This
Leandro Martı́nez,
Paul Webb,
Igor Polikarpov
et al.
(2005).
Molecular Dynamics Simulations of Ligand Dissociation from Thyroid Hormone Receptors: Evidence of the Likeliest Escape Pathway and Its Implications for the Design of Novel Ligands.
Journal of Medicinal Chemistry
, 49
(1)
, 23-26.
https://doi.org/10.1021/jm050805n
Identifiers
- DOI
- 10.1021/jm050805n