Sampling Molecular Conformers in Solution with Quantum Mechanical Accuracy at a Nearly Molecular-Mechanics Cost

J Chem Theory Comput. 2016 Sep 13;12(9):4385-9. doi: 10.1021/acs.jctc.6b00470. Epub 2016 Aug 26.

Abstract

We introduce a method to evaluate the relative populations of different conformers of molecular species in solution, aiming at quantum mechanical accuracy, while keeping the computational cost at a nearly molecular-mechanics level. This goal is achieved by combining long classical molecular-dynamics simulations to sample the free-energy landscape of the system, advanced clustering techniques to identify the most relevant conformers, and thermodynamic perturbation theory to correct the resulting populations, using quantum-mechanical energies from density functional theory. A quantitative criterion for assessing the accuracy thus achieved is proposed. The resulting methodology is demonstrated in the specific case of cyanin (cyanidin-3-glucoside) in water solution.

MeSH terms

  • Anthocyanins / chemistry*
  • Glucosides / chemistry*
  • Models, Molecular*
  • Molecular Conformation
  • Quantum Theory*
  • Thermodynamics
  • Water / chemistry*

Substances

  • Anthocyanins
  • Glucosides
  • cyanidin-3-O-beta-glucopyranoside
  • Water