Relationship among ligand conformations in solution, in the solid state, and at the Hsp90 binding site: geldanamycin and radicicol.

Relationship among ligand conformations in solution, in the solid state, and at the Hsp90 binding site: geldanamycin and radicicol. Research Abstract Details 

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Relationship among ligand conformations in solution, in the solid state, and at the Hsp90 binding site: geldanamycin and radicicol. Abstract Text:

Pahk Thepchatri,Tomasso Eliseo,Daniel O Cicero,David Myles,James P Snyder,

The unknown effects of a receptor's environment on a ligand's conformation presents a difficult challenge in predicting feasible bioactive conformations, particularly if the receptor is ill-defined. The primary hypothesis of this work is that a structure's conformational ensemble in solution presents viable candidates for protein binding. The experimental solution profile can be achieved with the NAMFIS (NMR analysis of molecular flexibility in solution) method, which deconvolutes the average NMR spectrum of small flexible molecules into individual contributing conformations with varying populations. Geldanamycin and radicicol are structurally different macrocycles determined by X-ray crystallography to bind to a common site on the cellular chaperone heat shock protein 90 (Hsp90). Without benefit of a receptor structure, NAMFIS has identified the bioactive conformers of geldanamycin and radicicol in CDCl3 solution with populations of 4% and 21%, respectively. Conversely, docking the set of NAMFIS conformers into the unliganded proteins with GLIDE followed by MM-GBSA scoring reproduces the experimental crystallographic binding poses.

Relationship among ligand conformations in solution, in the solid state, and at the Hsp90 binding site: geldanamycin and radicicol. Publishing Authors By Initials

P Thepchatri,T Eliseo,DO Cicero,D Myles,JP Snyder,

For similar natural sciences: physics: thermodynamics research abstracts see: natural sciences: physics: thermodynamics research

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Relationship among ligand conformations in solution, in the solid state, and at the Hsp90 binding site: geldanamycin and radicicol. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of the American Chemical Society

VOLUME: 129

Page Numbers: 3127-34

Journal Abbreviation: J. Am. Chem. Soc.

ISSN: 0002-7863

DAY: 27

MONTH: 02

YEAR: 2007

Relationship among ligand conformations in solution, in the solid state, and at the Hsp90 binding site: geldanamycin and radicicol. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7503056

Relationship among ligand conformations in solution, in the solid state, and at the Hsp90 binding site: geldanamycin and radicicol. Keywords Mesh Terms:

KEYWORDS: Thermodynamics

MESH TERMS: methods

Chemical & Substance for Abstract: Relationship among ligand conformations in solution, in the solid state, and at the Hsp90 binding site: geldanamycin and radicicol. Information

Substance Name: geldanamycin

Registry Number: 30562-34-6

Grant and Affiliation Information for Relationship among ligand conformations in solution, in the solid state, and at the Hsp90 binding site: geldanamycin and radicicol.

AFFILIATION: Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA.

Country: United States

AGENCY: United States NHGRI

GRANT: 1 U54 HG003918-01

ACRONYM: HG

MEDLINETA: J Am Chem Soc

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