Rapid Protein–Ligand Costructures from Sparse NOE Data

Dipen Shah; Eiso Ab; Tammo Diercks; Mathias Hass; Nico Van Nuland; Gregg Siegal

Rapid Protein–Ligand Costructures from Sparse NOE Data

Dipen Shah, Eiso Ab, Tammo Diercks, Mathias Hass, Nico Van Nuland, Gregg Siegal

Department of Bio-engineering Sciences

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

Abstract

An efficient way to rapidly generate protein-ligand costructures based on solution-NMR using sparse NOE data combined with selective isotope labeling is presented. A docked model of the 27 kDa N-terminal ATPase domain of Hsp90 bound to a small molecule ligand was generated using only 21 intermolecular NOEs, which uniquely defined both the binding site and the orientation of the ligand. The approach can prove valuable for the early stages of fragment-based drug discovery.

Original language	English
Pages (from-to)	10786-10790
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	55
Issue number	23
Publication status	Published - 1 Nov 2012

Keywords

NMR

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title = "Rapid Protein–Ligand Costructures from Sparse NOE Data",

abstract = "An efficient way to rapidly generate protein-ligand costructures based on solution-NMR using sparse NOE data combined with selective isotope labeling is presented. A docked model of the 27 kDa N-terminal ATPase domain of Hsp90 bound to a small molecule ligand was generated using only 21 intermolecular NOEs, which uniquely defined both the binding site and the orientation of the ligand. The approach can prove valuable for the early stages of fragment-based drug discovery.",

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author = "Dipen Shah and Eiso Ab and Tammo Diercks and Mathias Hass and {Van Nuland}, Nico and Gregg Siegal",

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T1 - Rapid Protein–Ligand Costructures from Sparse NOE Data

AU - Shah, Dipen

AU - Ab, Eiso

AU - Diercks, Tammo

AU - Hass, Mathias

AU - Van Nuland, Nico

AU - Siegal, Gregg

PY - 2012/11/1

Y1 - 2012/11/1

N2 - An efficient way to rapidly generate protein-ligand costructures based on solution-NMR using sparse NOE data combined with selective isotope labeling is presented. A docked model of the 27 kDa N-terminal ATPase domain of Hsp90 bound to a small molecule ligand was generated using only 21 intermolecular NOEs, which uniquely defined both the binding site and the orientation of the ligand. The approach can prove valuable for the early stages of fragment-based drug discovery.

AB - An efficient way to rapidly generate protein-ligand costructures based on solution-NMR using sparse NOE data combined with selective isotope labeling is presented. A docked model of the 27 kDa N-terminal ATPase domain of Hsp90 bound to a small molecule ligand was generated using only 21 intermolecular NOEs, which uniquely defined both the binding site and the orientation of the ligand. The approach can prove valuable for the early stages of fragment-based drug discovery.

KW - NMR

M3 - Article

SN - 0022-2623

VL - 55

SP - 10786

EP - 10790

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 23

ER -

Rapid Protein–Ligand Costructures from Sparse NOE Data

Abstract

Keywords

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