Mutation of amino acid residues at protein-protein interfaces alters the binding affinity of protein-protein complexes and may lead to diseases. In this study, we have systematically analysed the relationship between the changes in binding affinity upon amino acid substitutions and the effect of mutations as disease-causing or neutral. We observed that a large proportion of disease-causing mutations decrease the binding affinity in all the considered datasets such as (i) experimentally known binding affinity and disease causing mutations, (ii) experimentally known binding affinity and predicted effects of mutations, and (iii) experimentally known disease causing mutations and predicted binding affinity. However, this relationship depends on the disease class, and the statistics indicate that factors other than binding affinity are also influencing the disease development. Further, structural analysis of protein-protein complexes revealed that disease-causing mutations are mainly attributed with the disruption of non-covalent interactions. In certain cancers, several mutations increase the binding affinity and they may have been selected to enhance cell survival and growth. Further, incorporating the effects of mutations on binding affinity in protein-protein interaction network studies may enable researchers to deduce the mechanisms of specific diseases and also help to identify novel drug targets.

蛋白质-蛋白质界面的氨基酸残基突变会改变蛋白质-蛋白质复合物的结合亲和力，并可能导致疾病。在这项研究中，我们已经系统地分析了氨基酸取代上的结合亲和力的变化与致病或中性突变的影响之间的关系。我们观察到，在所有考虑的数据集中，很大一部分致病突变会降低结合亲和力，例如（i）实验已知的结合亲和力和致病突变，（ii）实验已知的结合亲和力和突变的预期效应，以及（iii ）实验已知的引起突变的疾病和预测的结合亲和力。但是，这种关系取决于疾病类别，统计表明除结合亲和力以外的其他因素也影响疾病的发展。此外，蛋白质-蛋白质复合物的结构分析表明，致病突变主要归因于非共价相互作用的破坏。在某些癌症中，几种突变会增加结合亲和力，可能已选择它们来增强细胞存活和生长。此外，在蛋白质-蛋白质相互作用网络研究中纳入突变对结合亲和力的影响可能使研究人员能够推断出特定疾病的机制，也有助于鉴定新的药物靶标。在某些癌症中，几种突变会增加结合亲和力，可能已选择它们来增强细胞存活和生长。此外，在蛋白质-蛋白质相互作用网络研究中纳入突变对结合亲和力的影响可能使研究人员能够推断出特定疾病的机制，也有助于鉴定新的药物靶标。在某些癌症中，几种突变会增加结合亲和力，可能已选择它们来增强细胞存活和生长。此外，在蛋白质-蛋白质相互作用网络研究中纳入突变对结合亲和力的影响可能使研究人员能够推断出特定疾病的机制，也有助于鉴定新的药物靶标。