Proteins exist as dynamic conformational ensembles. Here we suggest that the propensities of the conformations can be predictors of cell function. The conformational states that the molecules preferentially visit can be viewed as phenotypic determinants, and their mutations work by altering the relative propensities, thus the cell phenotype. Our examples include (i) inactive state variants harboring cancer driver mutations that present active state-like conformational features, as in K-Ras4B^G12V compared to other K-Ras4B^G12X mutations; (ii) mutants of the same protein presenting vastly different phenotypic and clinical profiles: cancer and neurodevelopmental disorders; (iii) alterations in the occupancies of the conformational (sub)states influencing enzyme reactivity. Thus, protein conformational propensities can determine cell fate. They can also suggest the allosteric drugs efficiency.

蛋白质作为动态构象整体存在。在这里，我们建议构象的倾向可以作为细胞功能的预测因子。分子优先访问的构象状态可以被视为表型决定因素，它们的突变通过改变相对倾向来发挥作用，从而改变细胞表型。我们的例子包括（i）包含癌症驱动突变的非活性状态变体，这些突变呈现活性状态样构象特征，如 K-Ras4B ^{G12V与其他 K-Ras4B G12X}突变相比；(ii) 同一蛋白质的突变体表现出截然不同的表型和临床特征：癌症和神经发育障碍；(iii) 影响酶反应性的构象（亚）态占据的变化。因此，蛋白质构象倾向可以决定细胞的命运。它们还可以表明变构药物的功效。