In proteins, the structural responses of a position to mutation rely on the Goldilocks principle: not too many links, not too few
| Autor: | Rodrigo Dorantes-Gilardi, Claire Lesieur, Lorenza Pacini, Laurent Vuillon, Laëtitia Bourgeat |
|---|---|
| Přispěvatelé: | Laboratoire de Mathématiques (LAMA), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Institut Rhône-Alpin des systèmes complexes (IXXI), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Ampère, Département Bioingénierie (BioIng), Ampère (AMPERE), École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Protein Conformation General Physics and Astronomy Computational biology Biology Molecular Dynamics Simulation Alternative protein 03 medical and health sciences Protein structure Position (vector) Animals Humans Physical and Theoretical Chemistry Amino Acids Databases Protein Sequence (medicine) chemistry.chemical_classification [SPI.NRJ]Engineering Sciences [physics]/Electric power Proteins Composition (combinatorics) Amino acid 030104 developmental biology chemistry Goldilocks principle Mutation (genetic algorithm) Mutation Algorithms |
| Zdroj: | Physical Chemistry Chemical Physics Physical Chemistry Chemical Physics, Royal Society of Chemistry, 2018, 20 (39), pp.25399-25410. ⟨10.1039/C8CP04530E⟩ Physical Chemistry Chemical Physics, 2018, 20 (39), pp.25399-25410. ⟨10.1039/C8CP04530E⟩ |
| ISSN: | 1463-9076 1463-9084 |
| DOI: | 10.1039/C8CP04530E⟩ |
| Popis: | International audience; A disease has distinct genetic and molecular hallmarks such as sequence variants that are likely to produce the alternative protein structures accountable for individual responses to drugs and disease development. Thus, to set up customized therapies, the structural influences of amino acids on one another need to be tracked down. Using network-based models and classical analysis of amino acid and atomic packing in protein structures, the influence of first shell neighbors on the structural fate of a position upon mutation, is revisited. Regardless of the type and position in a structure, amino acids satisfy on average over their neighbors, a low and similar number of atomic interactions, the average called the neighborhood watch (Nw). The structural tolerance of a position to mutation depends on the modulation of the composition and/or proximity of neighbors to maintain the same Nw, before and after mutation, at every position. Changes, upon mutation of the number of atomic interactions at the level of individual pairs (wij) are structurally tolerated but influence structural dynamics. Robust, fragile and rescue interactions can be identified with Nw and wij, offering a framework to classify sequence variants according to position-dependent structural changes. |
| Databáze: | OpenAIRE |
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