Simulation of nucleic acid dynamics and deformability during protein binding and damage recognition (C05)

• Subject Area: Biochemistry
• Term: from 2011 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 27112786

DNA damage is often recognized by an indirect readout mechanism of repair enzymes without formation of direct contacts with the repair enzyme. In the Molecular Dynamics simulation studies we plan to systematically investigate the deformability of DNA. This will be achieved by deforming the DNA along helical variables by restraining the terminal segments of a DNA in certain geometry. Combined with the Umbrella Sampling method it is then possible to extract free energy changes along helical and global variations of the DNA structure. In addition, we plan to employ weighted ensemble simulations to study the kinetics of conformational changes in nucleic acids and peptides. As model systems it is planned to use damaged DNA molecules recognized by repair enzymes MutM, XPA/Rad14 and Photolyases investigated experimentally in the SFB749.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 749: Dynamics and Intermediates of Molecular Transformations
• Applicant Institution: Ludwig-Maximilians-Universität München
• Co-Applicant Institution: Technische Universität München (TUM)
• Project Head: Professor Dr. Martin Zacharias