1. Bioinformatic analysis of the protein/DNA interface
- Author
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Daniel Svozil, Jiří Černý, Bohdan Schneider, Alexandre G. de Brevern, Agnel Praveen Joseph, Jean-Christophe Gelly, de Brevern, Alexandre G., Institute of Biotechnology AS CR, Laboratory of Informatics and Chemistry, Institute of Chemical Technology [Prague] (ICT), GR-Ex, Laboratoire d'Excellence, GR-Ex, Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Czech-France collaboration Barrande [MEB021032], BIOCEV CZ.1.05/1.1.00/02.0109 from the ERDF, [P305/ 80 12/1801] from the Czech Science Foundation, and institutional [AV0Z50520701], supported by [MSM 6046137302 to D.S. and P.Č.], and supported by the Ministry of Research (France), University Paris Diderot, Sorbonne Paris Cité (France), National Institute of Blood Transfusion (INTS, France), National Institute of Health and Medical Research (INSERM, France) and 'Investissements d'avenir', Laboratories of Excellence GR-Ex (France) (to J.C.G. and A.G.dB.). Funding for open access charge: Czech Science Foundation and Academy of Sciences of the Czech Republic.
- Subjects
Models, Molecular ,Protein Conformation ,DNA interface ,Crystal structure ,Plasma protein binding ,Pentapeptide repeat ,chemistry.chemical_compound ,0302 clinical medicine ,structural alphabet: Protein Blocks ,MESH: Protein Conformation ,Protein structure ,Structural Biology ,Structural motif ,Conformational isomerism ,[INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM] ,Genetics ,0303 health sciences ,[SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,MESH: DNA ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,DNA-Binding Proteins ,MESH: Nucleic Acid Conformation ,Naked DNA ,Data Interpretation, Statistical ,MESH: Phosphates ,MESH: Models, Molecular ,Protein Binding ,MESH: Computational Biology ,Stereochemistry ,Biophysics ,Biology ,DNA-binding protein ,Phosphates ,03 medical and health sciences ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,MESH: Water ,MESH: Protein Binding ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Transcription factor ,030304 developmental biology ,Computational Biology ,Water ,DNA structure ,DNA ,Base (topology) ,Crystallography ,chemistry ,protein structures ,Nucleic acid ,Nucleic Acid Conformation ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,DNA interactions ,protein ,MESH: Data Interpretation, Statistical ,030217 neurology & neurosurgery ,MESH: DNA-Binding Proteins - Abstract
Despite extensive studies of the geometry of protein/DNA interfaces the understanding of the affinity and specificity of the protein/DNA interactions remains elusive. We present a novel approach to geometric analysis of protein/nucleic acid interfaces that is based on classification of their local conformations. Protein structures are divided into a series of pentapeptide fragments and each is assigned one of 16 conformers or ‘protein blocks’ [de Brevern et al. Proteins 41, 271 (2000)]. Similarly, each DNA step (unit [base]sugar-phosphate-sugar[base]) is assigned one of ∼20 DNA conformers [Svozil et al. NAR 36, 3690 (2008)]. Significantly, local structures classified into distinct conformers can be represented by symbols so that they can be analyzed more easily than complicated 3D objects. Size of the fragments used for the classification allows analysis of structural features of the interface at a scale intermediate between too detailed interatomic contacts on one side and too crude protein motifs (helix-turn-helix, Zn-finger, ...) on the other. We will present correlations between protein and DNA conformers at their interface from more than 15 hundred protein/DNA crystal structures broken by various criteria of the analyzed structures as protein functional classification, e.g. in GO or Pfam or by crystallographic properties, resolution or overall structure quality.Acknowledgments. This work was supported by Czech-France collaboration Barrande (MEB021032) and Czech Science Foundation (P305/10/2184).
- Published
- 2013
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