Bio-mathematical aspects of the plasticity of proteins

Abstract : Proteins are biological objects made to resist perturbations and, atthe same time, adapt to new environments and new needs. What are thestructural properties of proteins allowing such plasticity? To tacklethis question we first model protein structure as a network of aminoacids and atoms in interaction. Given the 3D structural conformationof a mutation obtained In Silico, a network approachallows the quantification of its structural change. Using large setsof mutations, we concluded that structural change is independent fromthe type of amino acid replaced, or replacing after mutation. Lookingat the composition of amino acid neighborhoods, we noticed that thelocation of a type of amino acid in the 3D structure is arbitrary:meaning that constraints of amino acid interactions in a proteinshow to be position independent. Leading to theobservation that the position of the amino acid in the sequence is thesingle property modulating structural plasticity.The fact that amino acids can replace each other atany position because the interaction constraint is not dependent on thetype of amino acid,is based on the customization of neighbors via alternative amino acidmutations or compensatory mutations. Even if there is a large mutationtolerance based on structural robustness, mutations can have an impact onthe structural plasticity because of the change in strength of pairwsie interactionsand the distribution of atoms and neihgbors surrounding residues.The direct consequence of such a variable atomic packingdistribution, is a difference of void (empty space,no atoms) on the surface of residues as identified by some of my data/results.This raises the possibility that structural plasticity is not onlyregulated by amino acid and atomic contacts but also by carving localvoids within the protein structure to allow atomic motionsrequired for the function of the protein. Finally, to test this hypothesis, we haveimplemented three algorithms to measure the empty space around aminoacids to look at the relation between this empty space and structural plasticity.
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Rodrigo Dorantes Gilardi. Bio-mathematical aspects of the plasticity of proteins. Bioinformatics [q-bio.QM]. Université Grenoble Alpes, 2018. English. ⟨NNT : 2018GREAM092⟩. ⟨tel-02152862⟩

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