A- to B-DNA Transition in AMBER Force Fields and Its Coupling to Sugar Pucker.

Abstract

The A/B transition is a basic element of DNA conformational change. Because of its involvement in the sensing of the ionic conditions by DNA and in specific protein-DNA interactions, this transition is important for biological functions of DNA. Therefore, accurate modeling of the A/B equilibrium by means of empirical force fields is of utmost interest. In this work, we examine the A/B equilibrium in three AMBER force fields, including the recent bsc1 and OL15 modifications, using much longer MD simulations than attempted before. Special attention is paid to the coupling of the A/B equilibrium with the south/north (S/N) transition of the sugar pucker. We found that none of the tested force fields provided a satisfactory description of the A/B equilibrium because the B-form was predicted to be much too stable and the A-form was predicted to be almost absent even in concentrated trifluoroethanol solutions. Based on comparison with NMR data for duplexes and single nucleosides, we hypothesize that this problem arose from the incorrect description of the S/N equilibrium of sugar pucker, where the south conformation is much too stable, thus stabilizing the B-form. Because neither the A/B equilibrium in duplexes nor the S/N equilibrium in nucleosides was described accurately, further refinements of the AMBER DNA force fields are needed.