A Structural-Based Strategy for Recognition of Transcription Factor Binding Sites

Abstract

Scanning through genomes for potential transcription factor binding sites (TFBSs) is becoming increasingly important in this post-genomic era. The position weight matrix (PWM) is the standard representation of TFBSs utilized when scanning through sequences for potential binding sites. However, many transcription factor (TF) motifs are short and highly degenerate, and methods utilizing PWMs to scan for sites are plagued by false positives. Furthermore, many important TFs do not have well-characterized PWMs, making identification of potential binding sites even more difficult. One approach to the identification of sites for these TFs has been to use the 3D structure of the TF to predict the DNA structure around the TF and then to generate a PWM from the predicted 3D complex structure. However, this approach is dependent on the similarity of the predicted structure to the native structure. We introduce here a novel approach to identify TFBSs utilizing structure information that can be applied to TFs without characterized PWMs, as long as a 3D complex structure (TF/DNA) exists. This approach utilizes an energy function that is uniquely trained on each structure. Our approach leads to increased prediction accuracy and robustness compared with those using a more general energy function. The software is freely available upon request.

Molecular Recognition of Human Angiotensin-Coverting Enzyme I (hACE I) and Different Inhibitors

“…It means that if there is no crystal structure, the correct conformation can not be distinguished from other predicted conformations in the docking study. In the present study, based on our previous work [40][41][42][43][44][45], docking techniques were used to investigate the interaction conformations between the C-domain ACE and the traditional inhibitors (enalaprilat, captopril and lisinpriol), which are used for the treatment of hypertension, and compare the most possible interaction conformations with the crystal structures. In order to evaluate the dynamics of ACE docking and crystal conformations with the different ligands, the molecular dynamics simulations were performed.…”

Investigation Binding Patterns of Human Carboxylesterase I (hCES I) with Broad Substrates by MD Simulations

“…In addition, based on our previous work [109][110][111][112][113][114], the QM/MM methods based on the all-atom ab initio molecular dynamics have already successfully performed on many systems. Therefore, QM/MM technique also can be applied to study the catalytic mechanism more clearly.…”

ANFIS-based fuzzy systems for searching dna-protein binding sites

“…Contra v2 uses Multiz multiple sequence alignment Blanchette et al (2004) to identify conserved regions and has an extensive library of curated PWMs. On the other hand, the 3D structure of the TF protein was used to improve finding the 3D structure of the DNA sequences of K-mers and their flanking regions Xu et al (2013). More structural features can be calculated for Kmers to characterize functional TFBS from random background K-mers, e.g., PhysBinder computes some biophysical properties for the DNA bases to predict TFBSs Hooghe et al (2012); Broos et al (2013).…”