Efficient Free Energy Calculation of DNA Base Pair Distortion

Alfredo Peguero-Tejada and Arjan van der Vaart^*

Department of Chemistry, University of South Florida, 4202 East Fowler Avenue, CHE 205, Tampa, Florida 33620, United States

The six DNA base pair parameters (shear, stretch, stagger, buckle, propeller, and opening) which describe the relative rigid body translations and rotations of DNA bases are redefined without the use of any fitting procedure to an idealized structure, using simple vector algebra on only six atoms of the base pair. The new model values correlate very well with standard definitions and allow for a scheme to accurately and efficiently construct free energy profiles of DNA distortion using base pair parameters as reaction coordinates. The methodology is illustrated with umbrella sampling simulations along the propeller angles found in AX/XT DNA base steps and their uracil analogs. Strong correlations are found between propeller twisting and a number of conformational parameters, including buckle, opening, BI/BII backbone configuration, and sugar puckering. The thymine methyl group is observed to notably alter the local conformational free energy landscape, with effects within and directly upstream of the thymine containing base pair.