Experimental measurements of edge-to-face aromatic interactions have been used to test a series of molecular mechanics force fields. The experimental data were determined for a range of differently substituted aromatic rings using chemical double mutant cycles on hydrogen-bonded zipper complexes. These complexes were truncated for the purposes of the molecular mechanics calculations so that problems of conformational searching and the optimisation of large structures could be avoided. Double-mutant cycles were then carried out in silico using these truncated systems. Comparison of the experimental aromatic interaction energies and the X-ray crystal structures of these truncated complexes with the calculated data show that conventional molecular mechanics force fields (MM2, MM3, AMBER and OPLS) do not perform well. However, the XED force field which explicitly represents electron anisotropy as an expansion of point charges around each atom reproduces the trends in interaction energy and the three-dimensional structures exceedingly well. Collapsing the XED charges onto atom centres or the use of semi-empirical atom-centred charges within the XED force field gives poor results. Thus the success of XED is not related to the methods used to assign the atomic charge distribution but can be directly attributed to the use of off-atom centre charges.

An evaluation of force-field treatments of aromatic interactions

ZONTA, CRISTIANO
2002

Abstract

Experimental measurements of edge-to-face aromatic interactions have been used to test a series of molecular mechanics force fields. The experimental data were determined for a range of differently substituted aromatic rings using chemical double mutant cycles on hydrogen-bonded zipper complexes. These complexes were truncated for the purposes of the molecular mechanics calculations so that problems of conformational searching and the optimisation of large structures could be avoided. Double-mutant cycles were then carried out in silico using these truncated systems. Comparison of the experimental aromatic interaction energies and the X-ray crystal structures of these truncated complexes with the calculated data show that conventional molecular mechanics force fields (MM2, MM3, AMBER and OPLS) do not perform well. However, the XED force field which explicitly represents electron anisotropy as an expansion of point charges around each atom reproduces the trends in interaction energy and the three-dimensional structures exceedingly well. Collapsing the XED charges onto atom centres or the use of semi-empirical atom-centred charges within the XED force field gives poor results. Thus the success of XED is not related to the methods used to assign the atomic charge distribution but can be directly attributed to the use of off-atom centre charges.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/152212
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