1. Discrete analysis of camelid variable domains: sequences, structures, and in-silico structure prediction
- Author
-
Frédéric Cadet, Nicolas K. Shinada, Olivier Bertrand, Floriane Noël, Alexandre G. de Brevern, Alain Malpertuy, Jean-Christophe Gelly, Jean-Philippe Meyniel, Tarun Jairaj Narwani, Akhila Melarkode Vattekatte, Université de La Réunion - Faculté des Sciences et Technologies (FST), Université de La Réunion (UR), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), 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), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP), Services and solutions for Research Informatics [Paris] (Discngine), Discngine S.A.S [Paris], Institut National de la Transfusion Sanguine [Paris] (INTS), Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), ISoft, Atragene (Atragene), Atragene, GR-Ex, Laboratoire d'Excellence, GR-Ex, PEACCEL, Ministry of Research (France)., University Paris Diderot, Sorbonne, Paris Cité (France)., Discngine, Paris, France., ANRT, France., Conseil Régional de la Réunion., The European Social Fund EU (ESF)., French National Computing Centre CINES under grant no. A0010707621 by the GENCI (Grand Equipement National de Calcul Intensif)., French National Computing Centre CINES under grant no. A0040710426 by the GENCI (Grand Equipement National de Calcul Intensif)., University of La Réunion, Réunion Island (France)., National Institute for Blood Transfusion (INTS, France)., National Institute for Health and Medical Research (INSERM, France)., Indo-French Centre for the Promotion of Advanced Research/CEFIPRA: 5302-2., ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), and ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011)
- Subjects
Bioinformatics ,Computer science ,[SDV]Life Sciences [q-bio] ,Structural alphabet ,In silico ,Bioinformatics Keywords Secondary structure ,Discrete analysis ,lcsh:Medicine ,Complementarity determining region ,Computational biology ,Subjects Biochemistry ,Biochemistry ,Antibodies ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Secondary structure ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Protein secondary structure ,Complementarity determining regions ,030304 developmental biology ,0303 health sciences ,Heavy chain ,Frameworks ,General Neuroscience ,lcsh:R ,030302 biochemistry & molecular biology ,General Medicine ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,3. Good health ,Template ,Complementarity (molecular biology) ,Sequence structure relationship ,Nanobodies ,General Agricultural and Biological Sciences - Abstract
Antigen binding by antibodies requires precise orientation of the complementarity- determining region (CDR) loops in the variable domain to establish the correct contact surface. Members of the family Camelidae have a modified form of immunoglobulin gamma (IgG) with only heavy chains, called Heavy Chain only Antibodies (HCAb). Antigen binding in HCAbs is mediated by only three CDR loops from the single variable domain (VHH) at the N-terminus of each heavy chain. This feature of the VHH, along with their other important features, e.g., easy expression, small size, thermo-stability and hydrophilicity, made them promising candidates for therapeutics and diagnostics. Thus, to design better VHH domains, it is important to thoroughly understand their sequence and structure characteristics and relationship. In this study, sequence characteristics of VHH domains have been analysed in depth, along with their structural features using innovative approaches, namely a structural alphabet. An elaborate summary of various studies proposing structural models of VHH domains showed diversity in the algorithms used. Finally, a case study to elucidate the differences in structural models from single and multiple templates is presented. In this case study, along with the above-mentioned aspects of VHH, an exciting view of various factors in structure prediction of VHH, like template framework selection, is also discussed.
- Published
- 2020