A combined computational and experimental approach for the analysis of the enantioselective potential of a new macrocyclic receptor for N-protected alpha-amino acids
A combined computational and experimental approach for the analysis of the enantioselective potential of a new macrocyclic receptor for N-protected alpha-amino acids
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.
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
2717-2728
Ragusa, A.
a502c9f2-a4cd-48e4-8f6d-a44d35e7be7c
Hayes, J.M.
7ae35967-41b2-45a8-a7a3-5689317c028d
Light, M.E.
cf57314e-6856-491b-a8d2-2dffc452e161
Kilburn, J.D.
266a563a-6076-4109-9436-1c66d0b02383
2007
Ragusa, A.
a502c9f2-a4cd-48e4-8f6d-a44d35e7be7c
Hayes, J.M.
7ae35967-41b2-45a8-a7a3-5689317c028d
Light, M.E.
cf57314e-6856-491b-a8d2-2dffc452e161
Kilburn, J.D.
266a563a-6076-4109-9436-1c66d0b02383
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), .
(doi:10.1002/chem.200601289).
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.
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Published date: 2007
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
Identifiers
Local EPrints ID: 54372
URI: http://eprints.soton.ac.uk/id/eprint/54372
ISSN: 0947-6539
PURE UUID: 9e00967b-b318-430d-948e-d3b147694eda
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Date deposited: 31 Jul 2008
Last modified: 16 Mar 2024 03:04
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Author:
A. Ragusa
Author:
J.M. Hayes
Author:
J.D. Kilburn
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