Efficient and effective exploration of molecular shapes for drug discovery

回顾过去，我们发现药物的发现可能是一个特殊而难以控制的过程。这方面的一个著名例子包括亚历山大·弗莱明（Alexander Fleming）在1928年发现青霉素，当时他的一个葡萄球菌培养板被污染，并开发了一种霉菌，产生了一个无细菌的圆圈。另一个著名的例子要追溯到1943年，当时化学家阿尔伯特·霍夫曼（Albert Hoffman）偶然服用了LSD-25，发现了麦角酸二乙胺（LSD-25）的仿精神作用。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。一篇研究意外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%是由于意外发现而发现的。然而，制药行业在发现潜在的药物化合物时必须克服的不仅仅是好运。一项研究表明，发现一种新药可能需要10至17年的时间。另一项研究的结果强调，开发一种新药的平均成本为13亿美元。此外，这一过程还包括对数千种可能的候选物质进行综合和测试。然而，化学合成提供了获得单一数量的类药物分子的途径，据估计，这些类药物分子的数量约为数万亿个，远远超过了高通量筛选等实验筛选技术的能力，这是可以理解的。

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.