A combined computational and experimental approach for the analysis of the enantioselective potential of a new macrocyclic receptor for N-protected alpha-amino acids


Ragusa, A., Hayes, J.M., Light, M.E. and Kilburn, J.D. (2007) A combined computational and experimental approach for the analysis of the enantioselective potential of a new macrocyclic receptor for N-protected alpha-amino acids. Chemistry-a European Journal, 13, (9), 2717-2728. (doi:10.1002/chem.200601289).

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Original Publication URL: http://dx.doi.org/10.1002/chem.200601289

Description/Abstract

A new macrocyclic receptor incorporating a thiourea moiety has been synthesised. Crystal structures of the macrocycle showed that the receptor has a rigid backbone but the thiourea moiety can orientate itself to bind to a DMSO solvent molecule. Force-field (MMFFs) calculations were performed to model the macrocycle and its binding properties with respect to N-protected amino acids, which were measured experimentally by NMR titration. Binding free energies were calculated by using the mode integration algorithm (MINTA) or free-energy perturbation (FEP). Excellent qualitative agreement with experiment was obtained. To further exploit the accuracy of the free-energy predictions for this system, the faster free-energy algorithm MINTA was used as a prediction tool to test the binding affinity of the macrocycle towards a series of several other amino acid derivatives, which speeded up considerably the screening process and reduced laboratory costs.

Item Type: Article
ISSNs: 0947-6539 (print)
Related URLs:
Keywords: dynamics simulations, conformational, stochastic dynamics, receptors, host-guest systems, , recognition, van-der-waals, binding free-energies, molecular-force field, molecular modeling,enantioselectivity, free-energy calculations, monte-carlo, mmff94, electrostatic parameters, , free-energies, molecular
Subjects: Q Science
Q Science > QD Chemistry
Divisions: University Structure - Pre August 2011 > School of Chemistry
ePrint ID: 54372
Date Deposited: 31 Jul 2008
Last Modified: 27 Mar 2014 18:37
URI: http://eprints.soton.ac.uk/id/eprint/54372

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