Overstretching of B-DNA with various pulling protocols: Appearance of structural polymorphism and S-DNA

Abstract

We report a structural polymorphism of the S-DNA when a canonical B-DNA is stretched under different pulling protocols and provide a fundamental molecular understanding of the DNA stretching mechanism. Extensive all atom molecular dynamics simulations reveal a clear formation of S-DNA when the B-DNA is stretched along the 3 ′ directions of the opposite strands (OS3) and is characterized by the changes in the number of H-bonds, entropy and free energy. Stretching along 5 ′ directions of the opposite strands (OS5) leads to force induced melting form of the DNA.Interestingly, stretching along the opposite ends of the same strand (SS) leads to a coexistence of both the S-and melted M-DNA structures. We also do the structural characterization of the S-DNA by calculating various helical parameters. We find that S-DNA has a twist of ∼ 10 degrees which corresponds to helical repeat length of ∼ 36 base pairs in close agreement with the previous experimental results. Moreover, we find that the free energy barrier between the canonical and overstretched states of DNA is higher for the same termini (SE) pulling protocol in comparison to all other protocols considered in this work. Overall, our observations not only reconcile with the available experimental results qualitatively but also enhance the understanding of different overstretched DNA structures.

Understanding enhanced mechanical stability of DNA in the presence of intercalated anticancer drug: Implications for DNA associated processes

“…This is the "B-to-S" transition-a dsDNA present in the B-form when overstretched goes to an extended conformation called S-DNA 15,18 -that has been confirmed in both experiments 16,64,65 and simulations. 63,66 Here, we find that the intercalated drug-DNA complex adapts S-DNA like structure when pulled from the 3′-end of the DNA. Unlike the gradual decrease of NHB as for the SE pulling protocol, NHB decreases slightly from its initial value up to the extension of 62 Å.…”

What do we know about DNA mechanics so far?

“…dsDNA has been studied in various conditions, such as unzipping, shearing, stretching, and under a torque, to mimic different biological scenarios [1]. These have provided increased insights to various interesting aspects of DNA such as emergence of S-DNA upon overstretching [5,10,51,52], modifications of DNA structural and mechanical properties under different environments such as drug intercalators [15 ], salts [17 ,46 ] and ionic liquids [26 ]. These information are the key inputs for DNA nanotechnological applications, enabling researchers to design various DNA nanostructures like DNA nanotubes [32,33 ] and DNA nanorobots for drug delivery [65], as well as in DNA nanoelectronics [51,52].…”

“…Moreover, the understanding of the mechanisms of the underlying DNA structural transitions has important implications for DNA-based nano-technological applications, such as rational drug design, programmable molecular machines, and DNA origami. Due to the advent of single-molecule manipulation techniques and theoretical/computational studies, significant progress has been made in understanding the structural, mechanical and elastic properties of DNA [1][2][3][4][5][6][7][8][9][10][11][12], as well as in understanding small-molecule interactions with DNA [13,14,15 ].…”

Toward a theory of mechanochemistry: Simple models from the very beginnings

“…It is known that different directions of an outer force can change the kind of the reaction path . This one applied to our model system means that the external force could be applied either in the x ‐ or in the y ‐direction.…”

“…For comparison we add the BBP y and the f y which are not in use here It is known that different directions of an outer force can change the kind of the reaction path. [23,41,43,53,54,[77][78][79][80][81] This one applied to our model system means that the external force could be applied either in the x-or in the y-direction. However, pulling along the symmetric…”