The effects of a single residue substitution on the protein backbone are frequently quite small but there are many other potential sources of structural variation for protein. We present here a methodology considering different sources of distortions in order to isolate the very effect of the mutation. To validate our methodology, we consider a well-studied family with many single mutants: the human lysozyme. Most of the perturbations are expected to be at the very localisation of the mutation, but in many cases the effects are propagated at long range. We show that the distances between the mutated residue and the 5% most disturbed residues, exponentially decreases. One third of the affected residues are in direct contact with the mutated position; the remaining two thirds are potential allosteric effects. We confirm the reliability of the residues assigned as significantly perturbed by comparing our results to experimental studies. We confirm with the present method all the previously identified perturbations. This study shows that mutations have long-range impact on protein backbone that can be detected, although the displacement of the affected atoms is small.

单个残基取代对蛋白质骨架的影响通常很小，但蛋白质结构变异还有许多其他潜在来源。我们在这里提出了一种考虑不同失真来源的方法，以隔离突变的影响。为了验证我们的方法，我们考虑了一个经过充分研究的具有许多单一突变体的家族：人类溶菌酶。大多数扰动预计会发生在突变的位置，但在许多情况下，影响会在远距离传播。我们表明突变残基和 5% 最受干扰的残基之间的距离呈指数下降。三分之一受影响的残基与突变位置直接接触；剩下的三分之二是潜在的变构效应。通过将我们的结果与实验研究进行比较，我们确认了被指定为显着扰动的残基的可靠性。我们用本方法确认所有先前确定的扰动。这项研究表明，尽管受影响原子的位移很小，但突变对可以检测到的蛋白质骨架具有长期影响。