  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.
