ThreaDNA

ThreaDNA predicts the contribution of DNA mechanics to the sequence selectivity of DNA-binding proteins across whole genomes.

Key Features:

• Mechanical Distortion Sensing: Estimates DNA response to mechanical distortion using high-resolution structures of protein–DNA complexes.
• Nanoscale Modeling: Employs an efficient nanoscale modeling technique with no adjustable parameters to calculate deformation energy profiles along whole genomes at base-pair resolution.
• Integration with Direct Selectivity: Integrates indirect (mechanical) predictions with direct sequence selectivity using a generalized form of position-weight matrices.
• Quantitative Decomposition: Separately quantifies distinct physical mechanisms contributing to sequence selectivity to distinguish mechanical versus direct contributions.
• Implementation: Provided as Python software.

Scientific Applications:

• Genome-wide sequence selectivity prediction: Predicts how DNA mechanics contributes to protein-DNA sequence selectivity across entire genomes.
• Nucleosome analysis: Analyzes nucleosome-associated DNA mechanics to improve predictions of sequence selectivity.
• Bacterial regulator selectivity: Assesses sequence selectivity of bacterial regulators such as Fis and CRP by combining mechanical deformation data with direct sequence motifs.

Methodology:

Estimates DNA response to mechanical distortion from high-resolution protein–DNA complex structures; applies an efficient nanoscale modeling technique with no adjustable parameters to compute base-pair-resolution deformation energy profiles along whole genomes; integrates mechanical predictions with a generalized form of position-weight matrices to combine indirect and direct selectivity.