Conformational sampling and ensemble generation by molecular dynamics simulations: 18‐Crown‐6 as a test case

Abstract

AbstractUsing the crown ether 18‐crown‐6 as a test system, molecular dynamics has been evaluated as a technique for conformational searching and thermodynamic ensemble generation. By running a series of 200 ps and 2 ns simulations, an “optimum” temperature range for conformational searching, i.e., the temperature at which one finds the largest number of low energy structures, was demonstrated to be dependent on the time interval at which one examines the structure. By considering conformational degeneracy and entropy with the rigid rotor harmonic oscillator approximation we have been able to demonstrate that the ensemble generated approaches thermodynamic equilibrium in about 6 ns of simulation. To our knowledge this is the first time this has been demonstrated for a complex organic molecule and it highlights the power and usefulness of molecular dynamics as a method for thermodynamic ensemble generation and conformational searching.