BIOPHYSICAL THEORY AND MODELING |
Are DNA Transcription Factor Proteins Maxwellian Demons?
Longhua Hu 1, Alexander Y. Grosberg 2* and Robijn Bruinsma 3
1 Physics Department, University of Minnesota
2 University of Minnesota
3 University of California - LA
* To whom correspondence should be addressed. E-mail: grosberg{at}physics.umn.edu.
Submitted on January 17, 2008
Revised on March 13, 2008
Accepted on 7 April 2008
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Abstract |
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Transcription Factor (TF) proteins rapidly locate unique target sites on long genomic DNA molecules - and bind to them - during gene regulation. The search mechanism is known to involve a combination of 3D diffusion through the bulk of the cell and 1D sliding diffusion along the DNA. It is believed that the surprisingly high target binding rates of TF proteins relies on conformational fluctuations of the protein between a mobile state that is insensitive to the DNA sequence and an immobile state that is sequence sensitive. Since TF are not able to consume free energy during their search to obtain DNA sequence information, the Second Law of Thermodynamics must impose a strict limit on the efficiency of passive search mechanisms. In this paper we use a simple model for the protein conformational fluctuations to obtain the shortest binding time consistent with thermodynamics. The binding time is minimized if the spectrum of conformational fluctuations that take place during the search is "impedance-matched" to the large-scale conformational change that takes place at the target site. For parameter values appropriate for bacterial TF, this minimum binding time is within an order of magnitude of a limiting binding time corresponding to an idealized protein with instant target recognition. Numerical estimates suggest that typical bacteria operate in this regime of optimized conformational fluctuations.
Key Words:
DNA, Maxwell Demon, Recognition, Thermodynamics, Transcription Factors
