Computational models for large-scale simulations of facilitated diffusion

Mol Biosyst. 2012 Nov;8(11):2815-27. doi: 10.1039/c2mb25201e. Epub 2012 Aug 15.

Abstract

The binding of site-specific transcription factors to their genomic target sites is a key step in gene regulation. While the genome is huge, transcription factors belong to the least abundant protein classes in the cell. It is therefore fascinating how short the time frame is that they require to home in on their target sites. The underlying search mechanism is called facilitated diffusion and assumes a combination of three-dimensional diffusion in the space around the DNA combined with one-dimensional random walk on it. In this review, we present the current understanding of the facilitated diffusion mechanism and identify questions that lack a clear or detailed answer. One way to investigate these questions is through stochastic simulation and, in this manuscript, we support the idea that such simulations are able to address them. Finally, we review which biological parameters need to be included in such computational models in order to obtain a detailed representation of the actual process.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Computer Simulation*
  • Facilitated Diffusion / physiology*
  • Humans
  • Protein Binding
  • Transcription Factors / metabolism

Substances

  • Transcription Factors