DNA melting and energetics of the double helix

Author:

Alexander Vologodskii  Maxim D. Frank-Kamenetskii  

Journal:

Physics of Life Reviews

Issue Date:

2018

Abstract(summary):

Abstract Studying melting and energetics of the DNA double helix has been one of the major topics of molecular biophysics over the past six decades. The main objective of this article is to overview the current state of the field and to emphasize that there are still serious gaps in our understanding of the issue. We start with a concise description of the commonly accepted theoretical model of the DNA melting. We then concentrate on studies devoted to the comparison with experiment of theoretically predicted melting profiles of DNAs with known sequences. For long DNA molecules, such comparison is significant from the basic-science viewpoint while an accurate theoretical description of melting of short duplexes is necessary for various very important applications in biotechnology. Several sets of DNA melting parameters, proposed within the framework of the nearest neighbor model, are compared and analyzed. The analysis leads to a conclusion that in case of long DNA molecules the consensus set of nearest neighbor parameters describes well the experimental melting profiles. Unexpectedly, for short DNA duplexes the same set of parameters hardly yields any improvement as compared to the simplest model, which completely ignores the effect of heterogeneous stacking. Possible causes of this striking observation are discussed. We then overview the issue of separation of base-pairing and base-stacking contributions into the double helix stability. The recent experimental attempts to solve the problem are extensively analyzed. It is concluded that the double helix is essentially stabilized by stacking interaction between adjacent base pairs. Base pairing between complementary pairs does not appreciably contribute into the duplex stability. In the final section of the article, kinetic aspects of the DNA melting phenomenon are discussed. The main emphasis is made on the hysteresis effects often observed in melting of long DNA molecules. It is argued that the phenomenon can be well described via an accurate theoretical treatment of the random-walk model of melting kinetics of an isolated helical segment in DNA. Highlights • The article overviews the current state of the field of DNA melting. Several sets of DNA melting parameters of the nearest neighbor model are compared and analyzed. • For long DNA molecules, the consensus set of parameters describes well the experimental melting profiles. • For short DNA duplexes, the consensus set hardly yields any improvement as compared to the default model, which completely ignores the effect of heterogeneous stacking. • Estimations of base-pairing and base-stacking contributions into the double helix stability show that DNA is essentially stabilized by stacking interaction between adjacent base pairs. • Kinetic aspects of DNA melting phenomenon are discussed. The main emphasis is on the hysteresis effects often observed in melting of long DNA molecules.

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