Efficient and effective exploration of molecular shapes for drug discovery

倒退一步突显出，药物发现可能是一个特殊且难以控制的过程。一个著名的例子包括亚历山大·弗莱明在1928年发现了青霉素，当时他的一个葡萄球菌培养皿受到污染，并产生了一种霉菌，形成了一个无菌的循环。另一个著名的例子可以追溯到1943年，当时化学家阿尔伯特·霍夫曼通过意外摄入发现了麦角酸二乙胺(LSD-25)的拟精神分裂作用。尽管这些例子很简短，但这些例子表明，在整个历史上，偶然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，市场上所有药物的5.8%是由于偶然发现的[2]。然而，制药业在发现潜在的药物化合物时必须克服的不仅仅是运气。一项研究表明，发现一种新药的任务可能需要10-17年[3]，另一项研究的结果突出表明，开发一种新药的平均成本为13亿美元[4]。此外，这一过程涉及对数千名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类药物分子的途径，据估计，这类药物分子的数量约为数千亿美元，可以理解的是，这远远超过了高通量筛选等实验性筛选技术的能力。

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.