Protein structural robustness to mutations: an in silico investigation

摘要: Proteins possess qualities of robustness and adaptability to perturbations such as mutations, but occasionally fail withstand them, resulting in loss function. Herein, the structural impact mutations is investigated independently functional impact. Primarily, we aim at understanding mechanisms pre-requisite for integrity. The changes due propagate from site mutation residues much more distant than typical scales chemical interactions, following a cascade mechanism. This can trigger dramatic or subtle ones, consistent with function disease emergence new functions. Robustness enhanced by producing alternative structures, good agreement view that proteins are dynamic objects fulfilling their functions set conformations. result, robust also coherent epistasis rescue generally, non-additive mutational effects compensatory mutations. To achieve this study, developed first algorithm, referred Amino Acid Rank (AAR), which follows associated entire protein structure quantifies so be ranked accordingly. Assessing paths opens possibility assuming secondary mechanisms.