Multilevel Parallelization of Software for Accurate Protein-Ligand Affinities

软件的多级并行化可实现准确的蛋白质-配体亲和力

• 批准号: 8217262
• 负责人: Simon Webb
• 金额: $ 69.4万
• 依托单位: VERACHEM, LLC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8217262
• 关键词: Acquired Immunodeficiency Syndrome; Active Sites; Affinity; Algorithms; Binding; Binding Proteins; Binding Sites; Biotechnology; Cataloging; Catalogs; Cereals; Chemicals; Code; Complex; Computer Assisted; Computer Systems; Computer software; Computers; Databases; Development; Disease; Docking; Drug resistance; Due Process; Emerging Technologies; Entropy; Enzymes; Feedback; Free Energy; Goals; HIV Protease; HIV Protease Inhibitors; Individual; Industry; Lead; Licensing; Ligands; Medicine; Methods; Modeling; Molecular; Molecular Conformation; Peptide Hydrolases; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Potential Energy; Price; Procedures; Process; Property; Proteins; Research; Research Contracts; Research Personnel; Running; Scientist; Scoring Method; Screening procedure; Small Business Innovation Research Grant; Solutions; Speed; Structure; Technology; Testing; Time; Variant; Virus; Work; base; computer cluster; computer program; design; drug candidate; drug discovery; flexibility; improved; insight; mutant; novel therapeutics; parallel computing; prevent; programs; protein structure; public health relevance; receptor; research study; scientific computing; shared memory; small molecule; stem; success; supercomputer; three dimensional structure; tool; trend; virtual

DESCRIPTION (provided by applicant): Many drugs are small molecules that act by binding to a specific protein and thus blocking or altering its actions. For example, the HIV protease inhibitors are important AIDS treatments that work by binding in the active site of the protease enzyme and preventing it from helping to make new viruses. When scientists identify a protein, like HIV protease, as being important in a disease process, a next step often is to determine its three-dimensional structure in great detail. This structure then provides valuable guidance to chemists trying to design a small molecule that will bind the protein tightly. However, even when they know the structure of the protein, there is still a lot of trial and error in designing a drug. Many researchers have worked on computer programs to help predict whether a given molecule will bind a given protein, but without much success. Now, new software that VeraChem has been developing over the last few years is giving very good results for this problem. However, the software takes a long time to run and would be far more useful if it were much faster. For example, if chemists had an idea for a new compound to try, they could get the answer in a minutes instead of a few days. They could use the method to quickly and cheaply test thousands of compounds in chemical catalogs. And they could check whether a compound that works against their protein would keep working against mutant forms of the protein and thereby avoid drug-resistance. Thus, a fast version of VM2 would be very useful and would be a valuable commercial product. Speeding up VeraChem's method, VM2, is not as simple as running it on a faster computer, because individual computers have not been getting much faster in recent years. What is changing, though, is that computers are being made with more and more processors. The goal of this project is to speed up VM2 enormously by spreading its computational work across large numbers of separate processors in a single computer, in a cluster of computers, and even in a video card. This is not a simple task, but researchers have been able to speed up related molecular calculations in this way, and we are confident the same can be done for VM2. PUBLIC HEALTH RELEVANCE: We want to let scientists design new medicines more quickly with a computer program. The problem is that the program takes too long to do its calculations. This project is to speed up the calculations by changing the program so that it can make a large number of computer processors to work together to calculate the answers in a short time.

描述（由申请人提供）：许多药物是通过与特定蛋白质结合并因此阻止或改变其作用的小分子。例如，HIV蛋白酶抑制剂是重要的辅助治疗方法，通过在蛋白酶的活跃部位结合并防止其帮助生产新病毒来起作用。当科学家将蛋白质（例如HIV蛋白酶）识别为在疾病过程中很重要时，下一步通常是详细确定其三维结构。然后，该结构为试图设计一种将紧密结合蛋白质的小分子的化学家提供了宝贵的指导。但是，即使他们知道蛋白质的结构，设计药物仍有很多反复试验。许多研究人员已经研究了计算机程序，以帮助预测一个给定的分子是否会结合给定的蛋白质，但不会成功。现在，Verachem在过去几年中一直开发的新软件正在为这个问题带来很好的结果。但是，该软件需要很长时间才能运行，并且如果速度快得多，将会更有用。例如，如果化学家有一个新化合物的想法，他们可以在几分钟而不是几天内得到答案。他们可以使用该方法快速，便宜地测试了化学目录中数千种化合物。他们可以检查是否有针对其蛋白质的化合物会继续对抗蛋白质突变形式，从而避免抗药性。因此，VM2的快速版本将非常有用，并且将是宝贵的商业产品。加速Verachem的方法VM2并不像在更快的计算机上运行它那样简单，因为近年来单个计算机的越来越快。但是，正在改变的是，计算机是通过越来越多的处理器制造的。该项目的目的是通过在一台计算机，一组计算机甚至视频卡中将其计算工作跨在一台计算机中的大量单独处理器中传播，从而大大加快VM2的速度。这不是一项简单的任务，但是研究人员已经能够以这种方式加快相关的分子计算，我们对VM2也可以做同样的事情。 公共卫生相关性：我们希望通过计算机程序更快地设计新药。问题在于该程序花费太长时间进行计算。该项目是通过更改程序来加快计算的速度，以便它可以使大量计算机处理器共同工作以在短时间内计算答案。