Efficient multidimensional free energy calculations for ab initio molecular dynamics using classical bias potentials

We present a method for calculating multidimensional free energy surfaces w ithin the limited time scale of a first-principles molecular dynamics schem e. The sampling efficiency is enhanced using selected terms of a classical force field as a bias potential. This simple procedure yields a very substa ntial increase in sampling accuracy while retaining the high quality of the underlying ab initio potential surface and can thus be used for a paramete r free calculation of free energy surfaces. The success of the method is de monstrated by the applications to two gas phase molecules, ethane and perox ynitrous acid, as test case systems. A statistical analysis of the results shows that the entire free energy landscape is well converged within a 40 p s simulation at 500 K, even for a system with barriers as high as 15 kcal/m ol. (C) 2000 American Institute of Physics. [S0021-9606(00)00836-9].