title: Analysis of the interface variability in NMR structure ensembles of protein-protein complexes.
abstract: NMR structures consist in ensembles of conformers, all satisfying the experimental restraints, which exhibit a certain degree of structural variability. We analyzed here the interface in NMR ensembles of protein-protein heterodimeric complexes and found it to span a wide range of different conservations. The different exhibited conservations do not simply correlate with the size of the systems/interfaces, and are most probably the result of an interplay between different factors, including the quality of experimental data and the intrinsic complex flexibility. In any case, this information is not to be missed when NMR structures of protein-protein complexes are analyzed; especially considering that, as we also show here, the first NMR conformer is usually not the one which best reflects the overall interface. To quantify the interface conservation and to analyze it, we used an approach originally conceived for the analysis and ranking of ensembles of docking models, which has now been extended to directly deal with NMR ensembles. We propose this approach, based on the conservation of the inter-residue contacts at the interface, both for the analysis of the interface in whole ensembles of NMR complexes and for the possible selection of a single conformer as the best representative of the overall interface. In order to make the analyses automatic and fast, we made the protocol available as a web tool at: https://www.molnac.unisa.it/BioTools/consrank/consrank-nmr.html.
authors.affiliation: CIRPeB, University of Naples "Federico II", via Mezzocannone 16, 80134 Naples, Italy; Department of Pharmacy, University of Naples "Federico II", via Mezzocannone 16, 80134 Naples, Italy; Institute of Biostructures and Bioimaging - CNR, via Mezzocannone, 16, 80134 Naples, Italy. Electronic address: luisa.calvanese@unina.it.
authors.forename: Luisa
authors.initials: L
authors.lastname: Calvanese
authors.affiliation: CIRPeB, University of Naples "Federico II", via Mezzocannone 16, 80134 Naples, Italy; Department of Pharmacy, University of Naples "Federico II", via Mezzocannone 16, 80134 Naples, Italy; Institute of Biostructures and Bioimaging - CNR, via Mezzocannone, 16, 80134 Naples, Italy. Electronic address: gabriella.dauria@unina.it.
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Auria
authors.affiliation: Computational Structural Biology Group, Bijvoet Center for Biomolecular Research, Faculty of Science-Chemistry, Utrecht University, Utrecht, Netherlands. Electronic address: a.vangone@uu.nl.
authors.forename: Anna
authors.initials: A
authors.lastname: Vangone
authors.affiliation: CIRPeB, University of Naples "Federico II", via Mezzocannone 16, 80134 Naples, Italy; Department of Pharmacy, University of Naples "Federico II", via Mezzocannone 16, 80134 Naples, Italy; Institute of Biostructures and Bioimaging - CNR, via Mezzocannone, 16, 80134 Naples, Italy. Electronic address: lucia.falcigno@unina.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Falcigno
authors.affiliation: Department of Sciences and Technologies, University Parthenope of Naples, Centro Direzionale Isola C4, I-80143 Naples, Italy. Electronic address: romina.oliva@uniparthenope.it.
authors.forename: Romina
authors.initials: R
authors.lastname: Oliva
mesh_terms: D008958:Models, Molecular; D062105:Molecular Docking Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D012984:Software
keywords: COCOMAPS; CONSRANK; Inter-residue contacts; Interface; NMR; Protein complex