Weight matrices for protein-DNA binding sites from a single co-crystal structure

Robert G. Endres and Ned S. Wingreen
Phys. Rev. E 73, 061921 – Published 28 June 2006

Abstract

Transcription-factor proteins bind to specific DNA sequences to regulate gene expression in cells. DNA-binding sites are often identified using weight matrices calculated from multiple known binding sites. However, in many cases the number of examples is limited. Here, we report on an atomistic method that starts from an x-ray co-crystal structure of the protein bound to one particular DNA sequence, and infers other binding sites, which are used to construct a weight matrix. The emphasis of the paper is on using the Wang-Landau Monte Carlo algorithm to efficiently sample high-affinity binding sites, which demonstrates that sampling can produce accurate weight matrices in analogy to bioinformatics approaches. For cases of low complexity, we compare to the exhaustive (but slow) dead-end elimination algorithm. To recover crystal binding sites, it is important to include bound water in the protein-DNA interface. Our approach can, in principle, even be applied when no native protein-DNA co-crystal structure is available, only the structure of a closely related homologous protein whose amino-acid sequence is changed to the protein of interest.

  • Figure
  • Figure
  • Figure
  • Figure
  • Figure
  • Figure
  • Received 21 November 2005

DOI:https://doi.org/10.1103/PhysRevE.73.061921

©2006 American Physical Society

Authors & Affiliations

Robert G. Endres1,2,* and Ned S. Wingreen2

  • 1NEC Laboratories America, Inc., Princeton, New Jersey 08540, USA
  • 2Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544-1014, USA

  • *Corresponding author. Email address: rendres@princeton.edu

Article Text (Subscription Required)

Click to Expand

References (Subscription Required)

Click to Expand
Issue

Vol. 73, Iss. 6 — June 2006

Reuse & Permissions
Access Options
Author publication services for translation and copyediting assistance advertisement

Authorization Required


×
×

Images

×

Sign up to receive regular email alerts from Physical Review E

Log In

Cancel
×

Search


Article Lookup

Paste a citation or DOI

Enter a citation
×