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

Leandro Martínez, Paul Webb, Igor Polikarpov, Munir S. Skaf

Research output: Contribution to journalArticle

62 Scopus citations

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 β-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.

Original languageEnglish (US)
Pages (from-to)23-26
Number of pages4
JournalJournal of Medicinal Chemistry
Volume49
Issue number1
DOIs
StatePublished - Jan 12 2006

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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