IN SILICO DESIGN OF HIGH-AFFINITY RECOMBINANT ANTIBODIES

目前，有一种趋势是从小药物分子治疗转向使用生物制品，如单抗。MAB疗法使用高度特异的抗体与特定的细胞或蛋白质结合，以刺激免疫系统摧毁或中和那些可能参与疾病进展的成分。在自然免疫反应中，早期抗体以低亲和力结合，并且对它们与哪种抗原结合的特异性较低。随着免疫反应的持续和对抗原的长期接触，由于抗体结合区的突变，抗体“成熟”。这导致结合亲和力的增加或减少。这为有效抗体的计算设计提供了一个蓝图，优点是我们不需要依赖纯粹的随机突变，而是可以通过我们对生物分子和抗原之间相互作用的理解来指导我们。在这个项目中，我们将使用各种生物分子模拟技术来研究结合过程，并设计突变结构来优化抗体与其抗原的结合，同时保持选择性。设计的抗体结构将被重组生产并进行实验测试，如果成功，我们的战略将产生具有巨大影响的新技术。该项目的工业合作伙伴将能够在他们的抗体组合中利用这项技术。

Currently there is a trend to move from small drug molecule therapy to use of biologics such as monoclonal antibodies (mAb). MAb therapy uses highly specific antibodies to bind to particular cells or proteins, in order to stimulate the immune system to destroy or neutralise those components that may be involved in disease progression. In a natural immune response, early antibodies bind with low affinity and are less specific about which antigen they bind to. As the immune response continues and there is long-term exposure to an antigen, the antibodies "mature", as a result of mutations in the binding regions of the antibodies. This leads to an increase or decrease in binding affinity. This provides a blueprint for the computational design of effective antibodies, with the advantage that we do not need to rely on purely random mutations but can be guided by our understanding of the interactions between biomolecules and antigens.In this project we will use a variety of biomolecular simulation techniques to study the binding process, and to design mutated structures to optimise the binding of the antibody to its antigen, whilst maintaining selectivity. The designed antibody structure will be produced recombinantly and tested experimentally, and if successful our strategy will yield new technology of immense impact. The industrial partner for this project will be able to utilise the technology in their portfolio of antibodies.