Predicting Conformations of Biomolecules: Application to a Noradrenaline Analogue

Abstract

A new theoretical method is shown to overcome major obstacles in the calculation of biomolecular conformation. The torsional path integral Monte Carlo (TPIMC) technique is applied to the free jet expansion of a noradrenaline structural analogue (2-amino-1-phenylethanol) and is shown to predict the experimentally observed conformer populations accurately. Standard theoretical techniques employing a harmonic approximation in the evaluation of thermodynamic quantities such as free energy are shown to be unreliable for the analysis of conformer populations in flexible molecules. The TPIMC method is a general approach to the thermodynamic simulation of large molecules that treats anharmonicity and quantum effects within the torsional degrees of freedom.