After a long pause, the adventure in the PERL programming language series continues with another example of biophysics and molecular biology science application.This time, we are going to make a program to model the effect of the temperature on DNA stability in solution.
The effect of temperature DNA structure integrity plays an important role in molecular biology applications. For example, the DNA amplification method based on polymerase (the PCR method) is based on a series of temperature cycles to separate the two strand of DNA to replicate. DNA primers are used to initiate the process and the knowledge of their melting temperature (Tm) play an important role in optimizing the DNA amplification process.
The first attempts to create a model of DNA thermodynamics date back to the beginnings of 1960. Studies pionered by the groups of Zimm [1] and Tinoco [2], have shown that the relative stability of a double-stranded DNA molecule depends primarily on the nature of the nearest-neighbor bases along the sequence. This finding brought to the formulation of a simple mathematical model (called the nearest-neighbor (NN) model) to predict relative stabilities of double stranded DNA according to the nucleotide sequence [see Cantor]. Subseguently, the NN model was further improved by the contribution of several research groups. In particular, Santalucia and co-workers. proposed a set of parameters for the NN model that provides an excellent prediction of the thermodynamic properties of short DNA homo oligonucleotides and are commonly used to calculate the stability of DNA primers used for PCR applications.
In this third article on PERL programming, I will give some indication on how to implement a simple version of the NN model. To make more fancy the programming task, we are also going to provide the program with a simple Graphical user interface using PERL/Tk.
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