title: Sequence-Specific Recognition of DNA by Proteins: Binding Motifs Discovered Using a Novel Statistical/Computational Analysis.
abstract: Decades of intensive experimental studies of the recognition of DNA sequences by proteins have provided us with a view of a diverse and complicated world in which few to no features are shared between individual DNA-binding protein families. The originally conceived direct readout of DNA residue sequences by amino acid side chains offers very limited capacity for sequence recognition, while the effects of the dynamic properties of the interacting partners remain difficult to quantify and almost impossible to generalise. In this work we investigated the energetic characteristics of all DNA residue-amino acid side chain combinations in the conformations found at the interaction interface in a very large set of protein-DNA complexes by the means of empirical potential-based calculations. General specificity-defining criteria were derived and utilised to look beyond the binding motifs considered in previous studies. Linking energetic favourability to the observed geometrical preferences, our approach reveals several additional amino acid motifs which can distinguish between individual DNA bases. Our results remained valid in environments with various dielectric properties.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Prague 6, Czech Republic.|Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University in Prague, Prague 2, Czech Republic.
authors.forename: David
authors.initials: D
authors.lastname: Jakubec
authors.affiliation: EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Roman A
authors.initials: RA
authors.lastname: Laskowski
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Prague 6, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Vondrasek
mesh_terms: D000225:Adenine / Q000737:chemistry / Q000378:metabolism; D020816:Amino Acid Motifs; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D019295:Computational Biology / Q000379:methods*; D018360:Crystallography, X-Ray; D003596:Cytosine / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D030562:Databases, Protein; D006147:Guanine / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013223:Statistics as Topic / Q000379:methods*; D013816:Thermodynamics; D013941:Thymine / Q000737:chemistry / Q000378:metabolism
chemical_list: D000596:Amino Acids; D004268:DNA-Binding Proteins; D006147:Guanine; D003596:Cytosine; D004247:DNA; D000225:Adenine; D013941:Thymine