Friday, October 26, 2007
Ballroom Posters (Greenville Hyatt Regency Hotel)
514

Assessing Mm/pbsa Calculations for Conformational Transitions in DNA

Allyn R. Brice, Dev P. Arya, and Brian N. Dominy. Clemson University, Clemson, SC

Methods for the calculation of free energy differences are of great interest in the field of biochemistry. Accurate and efficient prediction of free energy differences would lead to greater understanding of biological processes, and also development in drug design methodologies. Free energy methods can be divided into pathway methods, which are more rigorous, and end-point methods which are more approximate. Evaluation of MM/PBSA, an end-point free energy analysis method, is presented for the differentiation between the A-form and B-form conformations of DNA, using the CHARMM27 force field. Free energy results from MM/PBSA are compared with the results from a previous study by B. Roux et al., which used the Potential of Mean Force (PMF) pathway method. Our MM/PBSA calculations of the free energy difference between A-form and B-form are shown to be in very close agreement with the PMF result. The charmm force field's influence on these free energy calculations is established through a comparison to free energy components in MM/PBSA analysis, obtained from the AMBER force field. The influence of the solvent system is determined by comparing free energy differences derived from DNA simulations within TIP3P explicit solvent and Generalized Born implicit solvent (using the GBSW module in charmm). Simulations run in implicit solvent yield free energies very similar to the explicit solvent simulations. Several accepted structural properties of DNA, such as slide, x-displacement, pseudorotation, were used for establishing the conformation during the simulation.