ThreaDNA: predicting DNA mechanics’ contribution to sequence selectivity of proteins along whole genomes

• DOI: 10.1093/bioinformatics/btx634
• Publication Date: 2017-10-06T19:12:01Z
• Authors: Jasmin Cevost; Cédric Vaillant; Sam Meyer
• Keywords: Executable; Python; Graphical user interface

Abstract Motivation Many DNA-binding proteins recognize their target sequences indirectly, by sensing DNA’s response to mechanical distortion. ThreaDNA estimates this based on high-resolution structures of the protein–DNA complex interest. Implementing an efficient nanoscale modeling DNA deformations involving essentially no adjustable parameters, it returns profile deformation energy along whole genomes, at base-pair resolution, within minutes usual laptop/desktop computers. Our predictions can also be easily combined with estimations direct selectivity through a generalized form position-weight-matrices. The formalism is accessible wide audience. Results We demonstrate importance indirect readout for nucleosome as well bacterial regulators Fis and CRP. Combined contribution provided sequence motifs, significantly improves prediction selectivity, allows quantifying two distinct physical mechanisms underlying it. Availability implementation Python software available bioinfo.insa-lyon.fr, natively executable Linux/MacOS systems user-friendly graphical interface. Galaxy webserver version available. Supplementary information data are Bioinformatics online.