Institut de Biotecnologia i de Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Institut de Biotecnologia i de Biomedicina, Campus Universitari de Bellaterra, Cerdanyola, Barcelona, Spain.
Methods Mol Biol. 2022;2449:197-211. doi: 10.1007/978-1-0716-2095-3_8.
Proteins microenvironments modulate their structures. Binding partners, organic molecules, or dissolved ions can alter the protein's compaction, inducing aggregation or order-disorder conformational transitions. Surprisingly, bioinformatic platforms often disregard the protein context in their modeling. In a recent work, we proposed that modeling how pH affects protein net charge and hydrophobicity might allow us to forecast pH-dependent aggregation and conditional disorder in intrinsically disordered proteins (IDPs). As these approaches showed remarkable success in recapitulating the available bibliographical data, we made these prediction methods available for the scientific community as two user-friendly web servers. SolupHred is the first dedicated software to predict pH-dependent aggregation, and DispHred is the first pH-dependent predictor of protein disorder. Here we dissect the features of these two software applications to train and assist scientists in studying pH-dependent conformational changes in IDPs.
蛋白质微环境会调节其结构。结合伴侣、有机分子或溶解离子可以改变蛋白质的紧密度，诱导聚集或有序-无序构象转变。令人惊讶的是，生物信息学平台在建模时经常忽略蛋白质的上下文。在最近的一项工作中，我们提出，模拟 pH 如何影响蛋白质净电荷和疏水性，可能使我们能够预测在内在无序蛋白质 (IDPs) 中 pH 依赖性聚集和条件无序。由于这些方法在再现现有文献数据方面取得了显著的成功，我们将这些预测方法作为两个用户友好的网络服务器提供给科学界。SolupHred 是第一个专门用于预测 pH 依赖性聚集的软件，而 DispHred 是第一个 pH 依赖性蛋白质无序预测器。在这里，我们剖析了这两个软件应用程序的功能，以培训和协助科学家研究 IDPs 中的 pH 依赖性构象变化。
