Simulation Studies of Twist-Stretch Coupling in Nucleic Acids

Abstract

The helical structures of DNA and double stranded RNA and their chiral nature lead to very specific and interesting mechanical properties. One such property is the twist-stretch coupling which, in case of DNA, has been found to be important in biological processes like DNA-protein binding and DNA packaging in viruses. Naively, as suggested by a simple picture of wringing out a cloth, both DNA and RNA should be expected to lengthen when unwound. Recent experiments on single DNA molecules has shown, however, that B-DNA in fact counter-intuitively shortens when twisted over a range around its native structure. This negative twist-stretch coupling of DNA has also been observed in some single molecule DNA simulation studies. A recent experiment on double stranded RNA has revealed that unlike DNA, RNA shortens when unwound, revealing a surprising difference between otherwise chemically similar molecules.In our study, we plan to probe the twist-stretch coupling of both DNA and ds-RNA using atomistic MD simulations. We will use harmonic twist constraints on individual molecules of double stranded B-DNA, A-RNA as well as the left-handed double helix Z-DNA of various nucleotide sequences, and then plot applied twist v/s stretch to get the values of twist-stretch coupling. This combined with a detailed analysis of the resultant atomistic structures will enable us to shed further light into the molecular details of this surprising effect.