Modeling DNA Deformation

Abstract

Abstract:Deformations of DNA contribute to its essential biological function. In our laboratory, we have been studying both local and global deformations of DNA and their relationship to base sequence by molecular modeling and simulation techniques. In the current chapter, we first give an overview of the various approaches used in our laboratory to build DNA models and to control DNA deformations. Notably, we discuss the JUMNA program that uses internal and helicoidal variables, and also umbrella sampling free energy simulations used to follow DNA deformations. In the second part, we summarize the results these techniques enabled us to obtain, starting from the large scale deformations, such as stretching, twisting and bending, down to the more local changes involving base opening and flipping and backbone conformations. A separate section deals with the sequence specific recognition of DNA by proteins and the role of DNA deformation in the process. We hope to show the reader that theoretical studies can play a significant role in obtaining a better understanding of this fascinating biopolymer.

NMR Studies of DNA Support the Role of Pre-Existing Minor Groove Variations in Nucleosome Indirect Readout

“…Indeed, the backbone angles behave differently in free and bound DNAs, with in particular the emergence of numerous α/γ conformers typical of bound DNAs. 40,67,68 In our approach, the intrinsic BII propensities are considered reporters of helicoidal features, in particular, the minor groove width.…”