Department of Chemistry, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy.
J Chem Theory Comput. 2023 Aug 22;19(16):5315-5333. doi: 10.1021/acs.jctc.3c00513. Epub 2023 Aug 1.
The design of new biomolecules able to harness immune mechanisms for the treatment of diseases is a prime challenge for computational and simulative approaches. For instance, in recent years, antibodies have emerged as an important class of therapeutics against a spectrum of pathologies. In cancer, immune-inspired approaches are witnessing a surge thanks to a better understanding of tumor-associated antigens and the mechanisms of their engagement or evasion from the human immune system. Here, we provide a summary of the main state-of-the-art computational approaches that are used to design antibodies and antigens, and in parallel, we review key methodologies for epitope identification for both B- and T-cell mediated responses. A special focus is devoted to the description of structure- and physics-based models, privileged over purely sequence-based approaches. We discuss the implications of novel methods in engineering biomolecules with tailored immunological properties for possible therapeutic uses. Finally, we highlight the extraordinary challenges and opportunities presented by the possible integration of structure- and physics-based methods with emerging Artificial Intelligence technologies for the prediction and design of novel antigens, epitopes, and antibodies.
设计能够利用免疫机制治疗疾病的新生物分子是计算和模拟方法面临的主要挑战。例如，近年来，抗体作为一类针对多种病理的重要治疗药物出现。在癌症中，由于对肿瘤相关抗原及其与人体免疫系统相互作用或逃避的机制有了更好的理解，免疫启发式方法正在得到迅猛发展。在这里，我们提供了用于设计抗体和抗原的主要最新计算方法的概述，同时，我们还回顾了用于鉴定 B 细胞和 T 细胞介导反应的表位的关键方法。特别关注描述基于结构和物理的模型，这些模型优于纯粹基于序列的方法。我们讨论了将具有定制免疫特性的生物分子工程化的新方法的意义，这些方法可能具有治疗用途。最后，我们强调了将基于结构和物理的方法与新兴人工智能技术相结合，用于预测和设计新型抗原、表位和抗体所带来的非凡挑战和机遇。
