title: Molecular properties from conformational ensembles. 1. Dipole moments of molecules with multiple internal rotations.
abstract: We present a novel method for constructing the stable conformational space of small molecules with many rotatable bonds that uses our iterative stochastic elimination (ISE) algorithm, a robust stochastic search method capable of finding ensembles of best solutions for large combinatorial problems. To validate the method, we show that ISE reproduces the best conformers found in a fully exhaustive search, as well as compare computed dipole moments to experimental values, based on molecular ensembles and their Boltzmann distributions. Results were also compared to the alternative molecular dynamics and simulated annealing methods. Our results clarify that many low energy conformations may be required to reproduce molecular properties, while single low energy conformers or ensembles of low energy conformers cannot account for the experimental properties of flexible molecules. Whereas ISE well reproduces conformations that are not separated by very large energy barriers, it has not been successful in reproducing conformations of strained molecules.
authors.affiliation: Laboratory of Molecular Modeling and Drug Design, Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Lavy
authors.forename: Daniel
authors.initials: D
authors.lastname: Harries
authors.forename: Amiram
authors.initials: A
authors.lastname: Goldblum
mesh_terms: D000465:Algorithms; D008958:Models, Molecular; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D012399:Rotation