Simulation studies of the structure and energies of a host-guest system
Simulation studies of the structure and energies of a host-guest system
Computer simulations are used to understand the binding behaviour of a number of amino acid derivatives in macrobicycle 12 in chloroform. Previous experimental work on this system indicated that macrobicycle 12, as well as being enantioselective for L amino acid derivatives, was able to stabilise the amide bond of the amino acid derivatives in the cis conformation. Monte Carlo (MC) simulations and free energy perturbation (FEP) calculations were able to successfully reproduce the observed behaviour. A detailed analysis was performed to rationalise the selectivity. In the course of this work, a methodology was developed that made feasible the simulations on the macrobicycle 12 system. The development of a novel MC sampling procedure and the replacement of explicit solvent by the GB/SA continuum model were found necessary to carry out realistic simulations. A new charge derivation called REPD was developed to produce OPLS-like charges by fitting to the molecular electrostatic potential. Free energies of hydration were calculated to test both REPD charges and the relative performance of the FEP and the linear interaction free energy methods.
University of Southampton
1999
Henchman, Richard Humfry
(1999)
Simulation studies of the structure and energies of a host-guest system.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Computer simulations are used to understand the binding behaviour of a number of amino acid derivatives in macrobicycle 12 in chloroform. Previous experimental work on this system indicated that macrobicycle 12, as well as being enantioselective for L amino acid derivatives, was able to stabilise the amide bond of the amino acid derivatives in the cis conformation. Monte Carlo (MC) simulations and free energy perturbation (FEP) calculations were able to successfully reproduce the observed behaviour. A detailed analysis was performed to rationalise the selectivity. In the course of this work, a methodology was developed that made feasible the simulations on the macrobicycle 12 system. The development of a novel MC sampling procedure and the replacement of explicit solvent by the GB/SA continuum model were found necessary to carry out realistic simulations. A new charge derivation called REPD was developed to produce OPLS-like charges by fitting to the molecular electrostatic potential. Free energies of hydration were calculated to test both REPD charges and the relative performance of the FEP and the linear interaction free energy methods.
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Published date: 1999
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Local EPrints ID: 464004
URI: http://eprints.soton.ac.uk/id/eprint/464004
PURE UUID: ab334839-1662-4e96-9f20-e1e85b70782c
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Date deposited: 04 Jul 2022 21:00
Last modified: 04 Jul 2022 21:00
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Author:
Richard Humfry Henchman
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