title: A new method for evaluating the specificity of indirect readout in protein-DNA recognition.
abstract: Proteins recognize a specific DNA sequence not only through direct contact (direct readout) with base pairs but also through sequence-dependent conformation and/or flexibility of DNA (indirect readout). However, it is difficult to assess the contribution of indirect readout to the sequence specificity. What is needed is a straightforward method for quantifying its contributions to specificity. Using Bayesian statistics, we derived the probability of a particular sequence for a given DNA structure from the trajectories of molecular dynamics (MD) simulations of DNAs containing all possible tetramer sequences. Then, we quantified the specificity of indirect readout based on the information entropy associated with the probability. We tested this method with known structures of protein-DNA complexes. This method enabled us to correctly predict those regions where experiments suggested the involvement of indirect readout. The results also indicated new regions where the indirect readout mechanism makes major contributions to the recognition. The present method can be used to estimate the contribution of indirect readout without approximations to the distributions in the conformational ensembles of DNA, and would serve as a powerful tool to study the mechanism of protein-DNA recognition.
authors.affiliation: Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan. s.yamasaki@aist.go.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamasaki
authors.forename: Tohru
authors.initials: T
authors.lastname: Terada
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kono
authors.forename: Kentaro
authors.initials: K
authors.lastname: Shimizu
authors.forename: Akinori
authors.initials: A
authors.lastname: Sarai
mesh_terms: D001483:Base Sequence; D001499:Bayes Theorem; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D017422:Sequence Analysis, DNA
chemical_list: D004268:DNA-Binding Proteins; D004247:DNA; D004706:Endodeoxyribonucleases; C064579:I-Ppo endonuclease