RaTrav: a tool for calculating mean first-passage times on biochemical networks

BMC Systems Biology

Paul A Bates²  Michal Kurzynski¹  Przemyslaw Chelminiak¹  Mieczyslaw Torchala² 

[1] Adam Mickiewicz University, Faculty of Physics, Umultowska 85, 61-614 Poznan, Poland;Biomolecular Modelling Laboratory, Cancer Research UK London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK

关键词: Free energy transduction;    Protein-protein docking;    Protein-protein interactions;    Protein-protein binding funnel;    Chemical kinetics;    Complex networks;    Hill’s method;    Monte Carlo method;    Stationary flux;    Mean first-passage time;    Random walk;    Master equation;    Markov processes;   

Others  :  1141710
DOI  :  10.1186/1752-0509-7-130

 received in 2013-04-26, accepted in 2013-11-13,  发布年份 2013

【 摘 要 】

Background

The concept of mean first-passage times (MFPTs) occupies an important place in the theory of stochastic processes, with the methods of their calculation being equally important in theoretical physics, chemistry and biology. We present here a software tool designed to support computational biology studies where Markovian dynamics takes place and MFPTs between initial and single or multiple final states in network-like systems are used. Two methods are made available for which their efficiency is strongly dependent on the topology of the defined network: the combinatorial Hill technique and the Monte Carlo simulation method.

Results

After a brief introduction to RaTrav, we highlight the utility of MFPT calculations by providing two examples (accompanied by Additional file 1) where they are deemed to be of importance: analysis of a protein-protein docking funnel and interpretation of the free energy transduction between two coupled enzymatic reactions controlled by the dynamics of transition between enzyme conformational states.

Conclusions

RaTrav is a versatile and easy to use software tool for calculating MFPTs across biochemical networks. The user simply prepares a text file with the structure of a given network, along with some additional basic parameters such as transition probabilities, waiting probabilities (if any) and local times (weights of edges), which define explicitly the stochastic dynamics on the network. The RaTrav tool can then be applied in order to compute desired MFPTs. For the provided examples, we were able to find the favourable binding path within a protein-protein docking funnel and to calculate the degree of coupling for two chemical reactions catalysed simultaneously by the same protein enzyme. However, the list of possible applications is much wider.

【 授权许可】

   
2013 Torchala et al.; licensee BioMed Central Ltd.

【 图 表 】

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