Taylor, C.G., Cullen, W., Collier, O.M. et al. (1 more author) (2017) A Quantitative Study of the Effects of Guest Flexibility on Binding Inside a Coordination Cage Host. Chemistry - A European Journal, 23 (1). pp. 206-213. ISSN 0947-6539
Abstract
We have performed a systematic investigation of the effects of guest flexibility on their ability to bind in the cavity of a coordination cage host in water, using two sets of isomeric aliphatic ketones that differ only in the branching patterns of their alkyl chains. Apart from the expected increase in binding strength for C9 over C7 ketones associated with their greater hydrophobic surface area, within each isomeric set there is a clear inverse correlation between binding free energy and guest flexibility, associated with loss of conformational entropy. This can be parameterized by the number of rotatable C-C bonds in the guest, with each additional rotatable bond resulting in a penalty of around 2 kJ mol(-1) in the binding free energy, in good agreement with values obtained from protein/ligand binding studies. We used the binding data for the new flexible guests to improve the scoring function that we had previously developed that allowed us to predict binding constants of relatively rigid guests in the cage cavity using the molecular docking programme GOLD (Genetic Optimisation of Ligand Docking). This improved scoring function resulted in a significant improvement in the ability of GOLD to predict binding constants for flexible guests, without any detriment to its ability to predict binding for more rigid guests.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | binding constants; coordination cage; host-guest chemistry; self-assembly; virtual screen |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Chemistry (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 25 Nov 2016 10:45 |
Last Modified: | 06 Mar 2017 16:29 |
Published Version: | https://doi.org/10.1002/chem.201604796 |
Status: | Published |
Publisher: | John Wiley & Sons |
Refereed: | Yes |
Identification Number: | 10.1002/chem.201604796 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:108460 |
Download
Filename: Taylor_et_al-2016-Chemistry_-_A_European_Journal.pdf
Licence: CC-BY 4.0