Computational modelling and simulation of antibodies to enhance binding affinity of a potential Burkholderia pseudomallei therapeutic

本博士提案旨在提高抗体：抗生素偶联物作为假伯克氏菌治疗的有效性，伯克氏菌是类鼻疽病的病原体和潜在的生物战剂。拟议的项目将结合实验室技术和计算模拟，以确定目前未知的单克隆抗体（mAb）和细菌的旁位和表位。随后，我的目标是提供一个合理设计的mAb，具有更好的结合亲和力。单克隆抗体的改进将对拟议的治疗产生直接影响；最终减少死亡人数，消除对长期抗生素制度的需求，并降低假芽孢杆菌作为生物武器的吸引力。

This PhD proposal aims to enhance the effectiveness of an antibody:antibiotic conjugate as a treatment for Burkholderia pseudomallei, the causative agent of melioidosis and a potential biological warfare agent. The proposed project will combine laboratory techniques and computational simulations with the goal of defining the currently unknown paratope and epitope of the monoclonal antibody (mAb) and bacteria. Subsequently, I will aim to deliver a rationally designed mAb with improved binding affinity. Improvements to the mAb would have a direct impact on the proposed treatment; ultimately reducing the number of deaths, removing the need for long term antibiotic regimes, and diminishing the attractiveness of B. pseudomallei as a bioweapon.