Benchmarks for flexible and rigid transcription factor-DNA docking

We constructed two benchmarks for flexible and rigid TF-DNA docking respectively using a unified non-redundant set of 38 test cases. The test cases encompass diverse fold families and are classified into easy and hard groups with respect to the degrees of difficulty in TF-DNA docking. The major parameters used to classify expected docking difficulty in flexible docking are the conformational differences between bound and unbound TFs and the interaction strength between TFs and DNA. For rigid docking in which the starting structure is a bound TF conformation, only interaction strength is considered.We believe these benchmarks are important for the development of better interaction potentials and TF-DNA docking algorithms, which bears important implications to structure-based prediction of transcription factor binding sites and drug design.Transcription factors (TFs) play key roles in the regulation of gene expression through binding to specific DNA sequences known as transcription factor binding sites (TFBSs) [1-3]. At the genomic level, the interactions between TFs and their binding sites in target genes (TGs) form multi-layered regulatory networks, in which TFs and TGs are represented as nodes and direct links between TFs and TGs correspond to regulatory interactions [4-7]. Although these transcriptional networks can be studied with one or more particular focuses, such as the structure, function, and/or evolution, the fundamental step in network construction is the identification of transcription factor binding sites. Computational identification of TFBSs on a genomic scale has been considered as a promising strategy for delineating these networks and remains one of the primary challenges in post-genomic bioinformatics [8,9]. Most of the current computational methodologies for TFBSs prediction are sequence-based; however structure-based TFBS prediction is gaining popularity [10-17]. Currently, structure-based approaches rely on resolved TF-DNA complex structures. D