Imperial College London
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ProfessorDavidKlug

Faculty of Natural Sciences, Department of Chemistry

Associate Dean for Enterprise for FoNS & Professor
 
 
 
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Contact

 

+44 (0)20 7594 5806d.klug

 
 
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Location

 

Molecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sowley:2019:10.1021/acs.jpcb.9b00501,
author = {Sowley, H and Liu, Z and Davies, J and Peach, R and Guo, R and Sim, S and Long, F and Holdgate, G and Willison, K and Zhuang, W and Klug, D},
doi = {10.1021/acs.jpcb.9b00501},
journal = {Journal of Physical Chemistry B},
pages = {3598--3606},
title = {Detection of drug binding to a target protein using EVV 2DIR spectroscopy},
url = {http://dx.doi.org/10.1021/acs.jpcb.9b00501},
volume = {123},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - We demonstrate that Electron-Vibration-Vibration Two Dimensional Infrared Spectroscopy (EVV 2DIR) can be used to detect the binding of a drug to a target protein active site. The EVV 2DIR spectrum of the FGFR1 Kinase target protein is found to have ~200 detectable crosspeaks in the spectral region 1250 - 1750cm-1/2600 - 3400cm-1, with an additional 63 caused by the addition of a drug, SU5402. Of these 63 new peaks, it is shown that only 6 are due to protein-drug interactions, with the other 57 being due to vibrational coupling within the drug itself. Quantum mechanical calculations employing density functional theory are used to support assignment of the 6 binding-dependent peaks, with one being assigned to a known interaction between the drug and a backbone carbonyl group which forms part of the binding site. None of the 57 intramolecular coupling peaks associated with the drug molecule change substantially in either intensity or frequency when the drug binds to the target protein. This strongly suggests that the structure of the drug in the target binding site, is essentially identical to that when it is not bound.
AU  - Sowley,H
AU  - Liu,Z
AU  - Davies,J
AU  - Peach,R
AU  - Guo,R
AU  - Sim,S
AU  - Long,F
AU  - Holdgate,G
AU  - Willison,K
AU  - Zhuang,W
AU  - Klug,D
DO  - 10.1021/acs.jpcb.9b00501
EP  - 3606
PY  - 2019///
SN  - 1520-5207
SP  - 3598
TI  - Detection of drug binding to a target protein using EVV 2DIR spectroscopy
T2  - Journal of Physical Chemistry B
UR  - http://dx.doi.org/10.1021/acs.jpcb.9b00501
UR  - https://pubs.acs.org/doi/10.1021/acs.jpcb.9b00501
UR  - http://hdl.handle.net/10044/1/67502
VL  - 123
ER  -
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