Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Warsaw, Poland.
Department of Chemistry, Iowa State University, Ames, IA, USA.
Methods Mol Biol. 2022;2340:17-40. doi: 10.1007/978-1-0716-1546-1_2.
Protein aggregation is a major hurdle in the development and manufacturing of protein-based therapeutics. Development of aggregation-resistant and stable protein variants can be guided by rational redesign using computational tools. Here, we describe the architecture and functionalities of the Aggrescan3D (A3D) standalone package for the rational design of protein solubility and aggregation properties based on three-dimensional protein structures. We present the case studies of the three therapeutic proteins, including antibodies, exploring the practical use of the A3D standalone tool. The case studies demonstrate that protein solubility can be easily improved by the A3D prediction of non-destabilizing amino acid mutations at the protein surfaces.
蛋白质聚集是蛋白质类治疗药物研发和生产的主要障碍。通过使用计算工具进行合理的重新设计，可以开发出抗聚集和稳定的蛋白质变体。在这里，我们描述了 Aggrescan3D（A3D）独立软件包的架构和功能，该软件包用于基于三维蛋白质结构对蛋白质的可溶性和聚集特性进行合理设计。我们展示了三种治疗性蛋白质（包括抗体）的案例研究，探索了 A3D 独立工具的实际应用。案例研究表明，通过 A3D 预测蛋白质表面的非稳定氨基酸突变，可以轻松提高蛋白质的可溶性。
