Designing a cross-disciplinary hit-to-lead platform for identifying optimum peptide-based antimicrobial therapeutics

抗菌肽（Antimicrobial Peptides，AMP）是一种潜在的替代经典抗生素的药物，在治疗全身性感染方面尚未取得突破性进展。我们将开发一个hit-to-lead平台，通过高性能计算提高吞吐量，以识别具有更高效力和选择性的先导候选肽。该电极导线将具有更高的体内治疗指数，将通过生物物理和生物化学实验方法进行评估。然后，我们将使用这个平台来研究这些先导化合物组合的协同效应，以确定针对革兰氏阳性菌或革兰氏阴性菌的最佳治疗“鸡尾酒”。

Antimicrobial peptides (AMPs) are a potential alternative to classical antibiotics that are yetto achieve a therapeutic breakthrough for treatment of systemic infections. We will develop ahit-to-lead platform, with throughput enhanced by high-performance computing, to identifylead candidate peptides with greater potency and selectivity. This lead will have a greater invivo therapeutic index, which will be evaluated through biophysical and biochemicalexperimental approaches. We will then use this platform to investigate the synergistic effectsof a combination of these leads in order to determine the best 'cocktail' of therapeutics whentargeting either Gram-positive or Gram-negative bacteria.