新冠药物筛选效率提升200倍 中国新一代天河超算入围戈登贝尔奖评选
2021-11-05 22:07:49 出处:快科技 作者:
宪瑞 编辑:宪瑞 人气: 4390 次 评论
(4)
11月5日晚,据央视报道,在天河新一代超级计算机上完成的“基于自由能微扰-绝对结合自由能方法的大规模新冠药物虚拟筛选”工作成功入围2021年度的戈登贝尔新冠特别奖,这是我国首次入围该特别奖奖项。
该成果由中国科学院上海药物所陈凯先院士、北京航空航天大学钱德沛教授和荷兰阿姆斯特丹大学Hans Westerhoff教授提名推荐。
通过利用天河新一代超级计算机的超大规模算力,使用国际领先的药物-靶标结合精准评价计算方法,实现了新冠应急药物(有效降低致死率和重症率)的快速筛选和发现。
团队以新冠病毒的M-Pro和TMPRSS2等重要靶点为研究对象,对来源于美国FDA(食药监局)批准上市及成熟商业库的近180万种小分子与靶点的复合物进行计算评价,在一周内完成了50余万个复杂分子动力学模拟任务,并筛选出98个化合物,其中50个化合物在生物活性测试中表现出较高活性,命中率达到51%,是当前国际最高水平。
计算筛选得到的双嘧达莫药物已完成100多例的临床试验,其结果表明:双嘧达莫干预三周后,
新冠重型患者临床症状明显改善,达到87.5%的出院率,明显优于对照组40%出院率,无死亡案例,无转成危重型案例,该药能提高治愈率并降低病亡率。
该药与阿比多尔合用后,新冠普通型患者的出院率为100%,平均出院时间为7天,比阿比多尔单用提前了4天,显示出良好的治疗效果。
根据实际测算,在天河新一代超级计算机的支撑下,基于自由能微扰-绝对结合自由能方法的药物筛选效能提升了200倍。
该项成果对于实现针对突发疫情的快速药物响应,具有极为重要的现实意义。
同时,基于天河新一代超级计算平台,天津超算中心还联合了天津中医药大学张伯礼院士团队开展治疗新冠的中药有效成分筛选工作,开展中药现代化研究。
戈登贝尔奖是国际上高性能计算应用领域的最高学术奖项,被称为“超算领域的诺贝尔奖”,由ACM每年评选和颁发,具有较大的国际影响力。
由于新冠疫情的暴发,ACM于2020年首次设立了戈登贝尔奖新冠特别奖(ACM Gordon Bell Special Prize for HPC-Based COVID-19 Research),以表彰在“超算抗疫”方面取得的杰出研究成果。
其评价的主要标准为:通过高性能计算的应用和创新,对理解疾病本质、控制疾病传播或发现有效治疗手段作出重要贡献。
2020年该奖项有6项成果入围,全部被美国包揽。
Machine translation:
Coronavirus drug screening efficiency increased by 200 times China's new generation of Tianhe supercomputers shortlisted for the Gordon Bell Prize
2021-11-05 22:07:49 From: Fast Technology Author: Xianrui Editor: Xianrui Popularity: 4390 times Comments(4)
On the evening of November 5, CCTV reported that the work of "Virtual Screening of Large-Scale Coronavirus Drugs Based on Free Energy Perturbation-Absolute Binding Free Energy Method" completed on the Tianhe New Generation Supercomputer was successfully shortlisted for the Gordon Bell coronavirus Special Award in 2021, which is the first time that China is shortlisted for this special award.
The work was nominated by Academician Kaixian Chen from the Shanghai Institute of Pharmaceutical Sciences of the Chinese Academy of Sciences, Professor Depei Qian from Beijing University of Aeronautics and Astronautics, and Professor Hans Westerhoff from the University of Amsterdam, the Netherlands.
The rapid screening and discovery of coronavirus emergency drugs (effective in reducing lethality and severe disease rates) was achieved by using the ultra-large scale computing power of the Tianhe next-generation supercomputer and using an internationally leading computational method for combined drug-target precision evaluation.
The team used important targets such as M-Pro and TMPRSS2 of coronavirus as research targets, and computationally evaluated nearly 1.8 million small molecule-target complexes from FDA-approved and mature commercial libraries, and completed more than 500,000 complex molecular dynamics simulation tasks within one week, and screened 98 compounds, among which 50 compounds showed high activity in biological activity tests with a hit rate of 51%, which is the highest level in the world today.
The results of the clinical trials of more than 100 cases of the computationally screened dipyridamole drug have been completed, which showed that after three weeks of dipyridamole intervention, the clinical symptoms of the coronavirus patients improved significantly, reaching a discharge rate of 87.5%, significantly better than the 40% discharge rate of the control group, with no cases of death and no cases of deterioration to critical, and that the drug improved the cure rate and reduced the death rate of the diseased.
After the drug was combined with Abirater, the discharge rate of patients with the coronavirus common type was 100%, and the average discharge time was 7 days, which was 4 days earlier than Abirater alone, showing good treatment effect.
According to the actual measurement, the efficacy of drug screening based on the free-energy perturbation-absolute binding free-energy method was improved by 200 times with the support of the Tianhe next-generation supercomputer.
The results are of great practical importance for achieving rapid drug response to unexpected outbreaks.
Meanwhile, based on the Tianhe new generation supercomputing platform, the Tianjin Supercomputing Center has also joined hands with the team of academician Zhang Boli of Tianjin University of Traditional Chinese Medicine to carry out the screening of active ingredients of traditional Chinese medicine for the treatment of coronavirus and to conduct research on the modernization of traditional Chinese medicine.
The Gordon Bell Award is the highest international academic award in the field of high-performance computing, known as the "Nobel Prize in supercomputing", selected and awarded by the ACM every year, with a large international influence.
The ACM Gordon Bell Special Prize for HPC-Based COVID-19 Research was established for the first time in 2020 due to the outbreak of the coronavirus epidemic to recognize outstanding research results in "supercomputing against the epidemic". The main criteria for evaluation are
The main criterion for the award is that the application of high performance computing and innovation has made a significant contribution to understanding the nature of disease, controlling the spread of disease, or discovering effective treatments.
In 2020, there were six finalists for this award, all of which were from the United States.
Translated with
www.DeepL.com/Translator (free version)