Efficient and effective exploration of molecular shapes for drug discovery

高效、有效地探索药物发现的分子形状

• 批准号: 2485445
• 金额: --
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2485445
• 关键词: Efficient; effective; exploration; molecular; shapes

Taking a step back in time highlights that drug discovery can be a peculiar and difficult process to control. A well-known example of this includes Alexander Fleming's discovery of penicillin in 1928, when one of his staphylococcus culture plates became contaminated and developed a mould that created a bacteria-free circle. Another famous example stems back to 1943 when the chemist Albert Hoffman discovered the psychotomimetic effect of lysergic acid diethylamide (LSD-25) via accidental consumption[1]. Although brief, these examples reveal that serendipity has played a significant role in the realm of drug discovery throughout history. One paper investigating the role of serendipity in anticancer drug discovery, states that 5.8% of all the drugs within the market were discovered as a result of serendipity[2]. However, it is not just good fortune that the pharmaceutical industry must overcome when tasked with discovering potential drug compounds. A study has shown that the task of discovering a new drug can take between 10 - 17 years[3] and the findings of another study has highlighted that the average cost of developing a new drug is 1.3 billion dollars[4]. Furthermore, this process involves the synthesising and testing of thousands of possible candidates. However, chemical synthesis provides access to a monolithic number of drug-like molecules, which can be estimated to be in the order of thousands of billions and understandably far exceeds the capacity of experimental screening techniques, such as high-throughput screening.

回顾过去，药物发现可能是一个特殊而难以控制的过程。一个著名的例子是亚历山大弗莱明在1928年发现了青霉素，当时他的一个培养皿被污染，并产生了一种霉菌，创造了一个无菌圈。另一个著名的例子可以追溯到1943年，当时化学家阿尔伯特霍夫曼发现了麦角酰二乙胺（LSD-25）通过意外消费的精神病效果[1]。虽然简短，但这些例子表明，在整个历史上，意外发现在药物发现领域发挥了重要作用。一篇研究偶然发现在抗癌药物发现中的作用的论文指出，市场上所有药物中有5.8%是由于偶然发现而发现的[2]。然而，制药行业在发现潜在药物化合物时必须克服的不仅仅是好运。一项研究表明，发现一种新药的任务可能需要10 - 17年[3]，另一项研究的结果强调，开发新药的平均成本为13亿美元[4]。此外，这个过程还涉及对数千个可能的候选人进行综合和测试。然而，化学合成提供了获得大量药物样分子的途径，这些药物样分子估计为数千亿的数量级，可以理解的是远远超过了实验筛选技术（例如高通量筛选）的能力。