Book of Abstracts: Albany 2005
Molecular Dynamics Simulation Studies on the Minor Groove Deformability of DNA
Conformational deformability of nucleic acids can influence its function and recognition by proteins. The TATA box binding protein is an example for a protein that binds to the minor groove of DNA and results in an opening of the minor groove and bending of the DNA towards the major groove. In order to investigate the molecular mechanism of minor groove deformations in DNA and the energetic contribution to the recognition process explicit solvent molecular dynamics (MD) simulations in combination with the umbrella sampling approach have been performed. As a reaction coordinate the distance between sugar atoms of two nucleotides on opposite strands was used. A similar reaction coordinate has already been employed in restraint energy minimization studies with an implicit solvent description (Lebrun & Lavery, Biopolymers 49, 341 (1999)). The MD simulations allow to calculate the free energy required to deform the DNA minor groove and can give an estimate on the contribution of DNA deformability to the recognition by a protein that binds to an opened minor DNA groove. Simulation studies were performed on two double stranded DNAs consisting of 12 base pairs and different central sequences (AAATTT and TATATA). The results indicate a significant sequence dependence of the calculated free energy of minor groove deformation and greater deformability of the TATATA vs. AAATTT sequence.
International University Bremen