Steroid hormone binding receptors: application of homology modeling, induced fit docking, and molecular dynamics to study structure-function relationships.
Steroid nuclear hormone binding receptors (SHRs) are ligand activated transcription factors involved in the regulation of target genes associated with key physiological and developmental processes. As such they are important targets for drug discovery. Crystal structures are now available for all members of the SHR family, however, earlier studies carried out using homology models proved to be quite valuable for understanding the binding of natural ligands and for designing novel therapeutic agents. The maleability of the binding pocket means that the crystal structure of an SHR in complex with one ligand may not suffice to explain the binding interactions of that same target with a different ligand. Consequently, induced fit docking and molecular dynamics are shown to be useful and necessary tools for understanding these receptors.
Cornell
Wendy
W
Chemistry Modeling and Informatics, Merck Research Laboratories, Rahway, NJ 07065, USA. wendy_cornell@merck.com
Nam
Kiyean
K
D003198:Computer Simulation; D055808:Drug Discovery; D008024:Ligands; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000187:drug effects; D013329:Structure-Activity Relationship
D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear