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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

基本信息

批准号：
8440752
负责人：
Simon Webb
金额：
$ 72.99万
依托单位：
VERACHEM, LLC
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2015-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8440752
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 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 screening shared memory small molecule stem success supercomputer three dimensional structure tool trend virtual

项目摘要

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.

描述(申请人提供)：许多药物是小分子，通过与特定蛋白质结合而起作用，从而阻断或改变其作用。例如，HIV蛋白酶抑制剂是重要的艾滋病治疗药物，它通过结合蛋白酶的活性部位，防止它帮助制造新的病毒而起作用。当科学家确定一种蛋白质，如艾滋病毒蛋白酶，在疾病过程中起重要作用时，下一步通常是非常详细地确定其三维结构。然后，这种结构为试图设计一种紧密结合蛋白质的小分子的化学家提供了有价值的指导。然而，即使他们知道了蛋白质的结构，在设计药物时仍然需要进行大量的试验和错误。许多研究人员已经开发了计算机程序来帮助预测给定的分子是否会与给定的蛋白质结合，但并不是很成功。现在，VeraChem在过去几年里一直在开发的新软件正在为这个问题提供非常好的结果。然而，该软件需要很长时间才能运行，如果速度快得多，它会更有用。例如，如果化学家有一个新化合物的想法可以尝试，他们可以在几分钟内得到答案，而不是几天。他们可以使用这种方法快速而廉价地测试化学目录中的数千种化合物。他们还可以检查一种对蛋白质起作用的化合物是否会继续对蛋白质的突变形式起作用，从而避免耐药性。因此，VM2的快速版本将非常有用，并将是一个有价值的商业产品。提高VeraChem的方法VM2的速度并不像在速度更快的计算机上运行那么简单，因为近年来，个别计算机并没有变得更快。然而，正在发生变化的是，制造计算机的处理器越来越多。该项目的目标是通过将计算工作分散到单个计算机、计算机集群甚至显卡中的大量独立处理器，从而极大地提高VM2的速度。这不是一项简单的任务，但研究人员已经能够通过这种方式加快相关分子计算的速度，我们有信心对VM2也能做到同样的事情。