Polymerase chain reaction: A Markov process approach

A probabilistic approach to the kinetics of the polymerase chain reaction ( PCR) is developed. The approach treats the primer extension step of PCR as a microscopic Markov process in which the molecules of deoxy-nucleoside tri phosphate (dNTP) are bound to the 3' end of the primer strand one at a time . The binding probability rates are prescribed by combinatorial rules in ac cord with the microscopic chemical kinetics. As an example, a simple model based on this approach is proposed and analysed, and an exact solution for the probability distribution of lengths of synthesized DNA strands is found by analytical means. Using this solution, it is demonstrated that the mode l is able to reproduce the main features of PCR, such as extreme sensitivit y to the variation of control parameters and the existence of an amplificat ion plateau. A multidimensional optimization technique is used to find nume rically the optimum values of control parameters which maximize the yield o f the target sequence for a given PCR run while minimizing the overall run time. (C) 1999 Academic Press.