scholarly journals Dynamic and Structural Modeling of the Specificity in Protein–DNA Interactions Guided by Binding Assay and Structure Data

2018 ◽  
Vol 14 (7) ◽  
pp. 3877-3889 ◽  
Author(s):  
Cheng Tan ◽  
Shoji Takada
Keyword(s):  
Structure Data ◽  
Binding Assay ◽  
Structural Modeling ◽  
Dna Interactions ◽  
Protein Dna Interactions

scholarly journals Dynamic and Structural Modeling of the Specificity in Protein-DNA Interactions Guided by Binding Assay and Structure Data

2018 ◽  
Author(s):  
Cheng Tan ◽  
Shoji Takada
Keyword(s):  
Structure Data ◽  
Dna Sequences ◽  
Complex Structure ◽  
Specific Protein ◽  
Coarse Grained ◽  
Binding Modes ◽  
Binding Assays ◽  
Dna Interactions ◽  
Protein Dna Interactions ◽  
Dynamics Simulations

ABSTRACTHow transcription factors (TFs) recognize their DNA sequences is often investigated complementarily by high-throughput protein binding assays and by structural biology experiments. The former quantifies the specificity of TF binding sites for numerous DNA sequences, often represented as the position-weight-matrix (PWM). The latter provides mechanistic insights into the interactions via the protein-DNA complex structures. However, these two types of data are not readily integrated. Here, we propose and test a new modeling method that incorporates the PWM with complex structure data. Based on pre-tuned coarse-grained models for proteins and DNAs, we model the specific protein-DNA interactions, PWMcos, in terms of an orientation-dependent potential function, which enables us to perform molecular dynamics simulations at unprecedentedly large scales. We show that the PWMcos model reproduces subtle specificity in the protein-DNA recognition. During the target search in genomic sequences, TF moves on highly rugged landscapes and occasionally flips on DNA depending on the sequence. The TATA-binding protein exhibits two remarkably distinct binding modes, of which frequencies differ between TATA-containing and TATA-less promoters. The PWMcos is general and can be applied to any protein-DNA interactions given their PWMs and complex structure data are available.

scholarly journals A CAPS-based binding assay provides semi-quantitative validation of protein-DNA interactions

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Yongyao Xie ◽  
Yaling Zhang ◽  
Xiucai Zhao ◽  
Yao-Guang Liu ◽  
Letian Chen
Keyword(s):  
Binding Assay ◽  
Dna Interactions ◽  
Protein Dna Interactions ◽  
Quantitative Validation

A polyplex qPCR-based binding assay for protein–DNA interactions

The Analyst ◽  
2012 ◽  
Vol 137 (18) ◽  
pp. 4111 ◽  
Author(s):  
Morgane J. J. Moreau ◽  
Patrick M. Schaeffer
Keyword(s):  
Binding Assay ◽  
Dna Interactions ◽  
Protein Dna Interactions
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