Related ArticlesScreening protein-small molecule interactions by NMR.
Methods Mol Biol. 2013;1008:389-413
Authors: Davis B
Abstract
Nuclear magnetic resonance (NMR) is well suited to probing the interactions between ligands and macromolecular receptors. It is a truly label-free technique, requiring only the presence of atoms (usually (1)H or (19)F) which give rise to observable resonances on either the ligand or the receptor. A number of parameters associated with these resonances can be used to distinguish rapidly tumbling compounds from ligands which bind to a macromolecular receptor. As such, NMR reports directly on the molecular components involved in the binding interaction whilst avoiding artifacts arising from the addition of an observable label. NMR is also unique amongst biophysical techniques in giving information on the chemical nature of almost all of the constituents present in the sample, thus allowing ready identification of sample, contaminants, degraded material and buffers. Solution phase NMR is also free of artifacts introduced by the presence of a solid support or matrix, although some interesting NMR techniques have been developed to identify ligand-receptor interactions in both solid and heterogeneous phase systems.NMR can readily report on molecular interactions across a wide range of affinities and timescales. Although NMR is not an inherently sensitive technique, the development of cryogenic probeheads over the past decade has dramatically increased the range of applicability of the technique and reduced the stringent sample requirements that used to be regarded as an "Achilles' heel" of NMR. The last, but by no means the least, NMR has the ability to determine structural information at atomic resolution; this has proved to be particularly useful when applied to those protein-ligand systems which cannot be readily crystallized.
[NMR paper] Small molecule binding sites on proteins established by paramagnetic NMR spectroscopy.
Small molecule binding sites on proteins established by paramagnetic NMR spectroscopy.
Related Articles Small molecule binding sites on proteins established by paramagnetic NMR spectroscopy.
J Am Chem Soc. 2013 Mar 20;
Authors: Guan JY, Keizers PH, Liu WM, Loehr F, Skinner SP, Heeneman EA, Schwalbe H, Ubbink M, Siegal GD
Abstract
Determining the three dimensional structure of a small molecule-protein complex with weak affinity can be a significant challenge. We present a paramagnetic NMR method to determine intermolecular structure...
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03-21-2013 02:58 PM
[NMR paper] NMR Methods for Detection of Small Molecule Binding to RGS4.
NMR Methods for Detection of Small Molecule Binding to RGS4.
Related Articles NMR Methods for Detection of Small Molecule Binding to RGS4.
Methods Enzymol. 2013;522:133-52
Authors: Storaska AJ, Neubig RR
Abstract
The duration and amplitude of G-protein-coupled receptor (GPCR) signaling is controlled by regulator of G-protein signaling (RGS) proteins. The 20 RGS family members act as GTPase accelerating proteins through their interaction with the G? subunit of the G??? heterotrimer. Their influence over GPCR signaling has attracted many to...
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02-05-2013 09:51 PM
[CNS Yahoo group] How to add bond between protein residue and a small molecule in CNS
How to add bond between protein residue and a small molecule in CNS
Dear All, I'm stuck in a step where in i need to connect a bond an amino acid residue and a small molecule in CNS Thank you. Joseph
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08-07-2011 01:35 AM
Preparation of protein samples for NMR structure, function, and small-molecule screening studies.
Preparation of protein samples for NMR structure, function, and small-molecule screening studies.
Preparation of protein samples for NMR structure, function, and small-molecule screening studies.
Methods Enzymol. 2011;493:21-60
Authors: Acton TB, Xiao R, Anderson S, Aramini J, Buchwald WA, Ciccosanti C, Conover K, Everett J, Hamilton K, Huang YJ, Janjua H, Kornhaber G, Lau J, Lee DY, Liu G, Maglaqui M, Ma L, Mao L, Patel D, Rossi P, Sahdev S, Shastry R, Swapna GV, Tang Y, Tong S, Wang D, Wang H, Zhao L, Montelione GT
In this chapter, we...
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03-05-2011 01:02 PM
[NMR paper] NMR structure of a complex between MDM2 and a small molecule inhibitor.
NMR structure of a complex between MDM2 and a small molecule inhibitor.
Related Articles NMR structure of a complex between MDM2 and a small molecule inhibitor.
J Biomol NMR. 2004 Oct;30(2):163-73
Authors: Fry DC, Emerson SD, Palme S, Vu BT, Liu CM, Podlaski F
MDM2 is a regulator of cell growth processes that acts by binding to the tumor suppressor protein p53 and ultimately restraining its activity. While inactivation of p53 by mutation is commonly observed in human cancers, a substantial percentage of tumors express wild type p53. In many of...
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11-24-2010 10:01 PM
[NMR paper] Exploring the active site of human factor Xa protein by NMR screening of small molecu
Exploring the active site of human factor Xa protein by NMR screening of small molecule probes.
Related Articles Exploring the active site of human factor Xa protein by NMR screening of small molecule probes.
Org Biomol Chem. 2003 Dec 7;1(23):4235-41
Authors: Fielding L, Fletcher D, Rutherford S, Kaur J, Mestres J
A collection of small molecules (MW < 350 Da) was screened for binding to human factor Xa using saturation transfer difference NMR spectroscopy to detect binding. The NMR screening experiments identified four hits. Binding isotherms...
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11-24-2010 09:16 PM
Novel Small Molecule Inhibitors of MDR Mycobacterium tuberculosis by NMR Fragment Scr
Novel Small Molecule Inhibitors of MDR Mycobacterium tuberculosis by NMR Fragment Screening of Antigen 85C.
Related Articles Novel Small Molecule Inhibitors of MDR Mycobacterium tuberculosis by NMR Fragment Screening of Antigen 85C.
J Med Chem. 2010 Nov 12;
Authors: Scheich C, Puetter V, Schade M
Protein target-based discovery of novel antibiotics has been largely unsuccessful despite rich genome information. Particularly in need are new antibiotics for tuberculosis, which kills 1.6 million people annually and shows a rapid increase in...
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11-16-2010 04:13 PM
Small Molecule NMR Scientist (B.S./ M.S.) at Novartis Ag (Cambridge, MA)
Small Molecule NMR Scientist (B.S./ M.S.) at Novartis Ag (Cambridge, MA)
using the state-of-the-art NMR methodologies. As an NMR scientist within the team, you will be responsible for ... in small molecular NMR with demonstrated success in modern NMR methodologies. Demonstrated skills in data collection...
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Screening protein-small molecule interactions by NMR.
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