Abstract
Renaturation of the complementary single strands of DNA is one of the important processes that requires better understanding in the view of molecular biology and biological physics. Here we develop a stochastic dynamical model on the DNA renaturation. According to our model there are at least three steps in the renaturation process viz. nonspecific-contact formation, correct-contact formation and nucleation, and zipping. Most of the earlier two-state models combined nucleation with nonspecific-contact formation step. In our model we suggest that it is considerably meaningful when we combine the nucleation with the zipping since nucleation is the initial step of zipping and nucleated and zipping molecules are indistinguishable. Nonspecific contact formation step is a pure three-dimensional diffusion controlled collision process. Whereas nucleation involves several rounds of one-dimensional slithering and internal displacement dynamics of one single strand of DNA on the other complementary strand in the process of searching for the correct-contact and then initiate nucleation. Upon nucleation, the stochastic zipping follows to generate a fully renatured double stranded DNA. It seems that the square-root dependency of the overall renaturation rate constant on the length of reacting single strands originates mainly from the geometric constraints in the diffusion controlled nonspecific-contact formation step. Further the inverse scaling of the renaturation rate on the viscosity of reaction medium also originates from nonspecific contact formation step. On the other hand the inverse scaling of the renaturation rate with the sequence complexity originates from the stochastic zipping which involves several rounds of crossing over the free-energy barrier at microscopic levels. When the sequence of renaturing single strands of DNA is repetitive with less complexity then the cooperative effects will not be noticeable since the parallel zipping will be a dominant enhancing factor. However for DNA strands with high sequence complexity and length one needs to consider the underlying cooperative effects both at microscopic and macroscopic levels to explain various scaling behaviours of the overall renaturation rate.
Highlights
The biological function of DNA depends largely on its double stranded helical structure and its ability to unwind and rewind in a reversible manner
The stochastic zipping follows to generate a fully renatured double stranded DNA. It seems that the square-root dependency of the overall renaturation rate constant on the length of reacting single strands originates mainly from the geometric constraints in the diffusion controlled nonspecific-contact formation step
The basic steps involved in the process of renaturation of c-ssDNA strands viz. (a) formation of nonspecific contact (b) nucleation or correct contact formation and (c) zippering can be well represented by Scheme III of Fig 2
Summary
The biological function of DNA depends largely on its double stranded helical structure and its ability to unwind and rewind in a reversible manner. Understanding the dynamics and mechanism of renaturation of c-ssDNAs in solution is important in recombination, design of primers for polymerase chain reaction, design of oligonucleotide probes for microarray chips, various membrane blotting techniques and other related DNA fingerprinting technologies [2,3,4,5]. In this context, several models describing the process of renaturation of c-ssDNAs in aqueous solution have been developed and experimentally verified [6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]. Detailed understanding of the mechanism of renaturation of c-ssDNA at microscopic level is one of the important contemporary topics of interest in molecular biology and biological physics
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