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：
7906160
负责人：
Simon Webb
金额：
$ 14.08万
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 2011-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7906160
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 Protein Binding 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

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. 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）：许多药物都是小分子，通过与特定蛋白质结合从而阻断或改变其作用而发挥作用。例如，HIV 蛋白酶抑制剂是重要的艾滋病治疗方法，它通过与蛋白酶的活性位点结合并阻止其帮助制造新病毒来发挥作用。当科学家确定一种蛋白质（如 HIV 蛋白酶）在疾病过程中发挥重要作用时，下一步通常是详细确定其三维结构。这种结构为试图设计紧密结合蛋白质的小分子的化学家提供了宝贵的指导。然而，即使他们知道蛋白质的结构，在设计药物时仍然需要进行大量的试验和错误。许多研究人员致力于开发计算机程序来帮助预测给定分子是否会结合给定蛋白质，但没有取得太大成功。现在，VeraChem 在过去几年中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，如果速度更快的话会更有用。例如，如果化学家有一个尝试新化合物的想法，他们可以在几分钟内而不是几天内得到答案。他们可以使用该方法快速且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抗其蛋白质的化合物是否会继续对抗该蛋白质的突变形式，从而避免耐药性。因此，VM2 的快速版本将非常有用，并且将是一个有价值的商业产品。加速 VeraChem 的方法 VM2 并不像在更快的计算机上运行那么简单，因为近年来个人计算机的速度并没有提高多少。然而，正在发生的变化是，计算机配备了越来越多的处理器。该项目的目标是通过将 VM2 的计算工作分散到单台计算机、计算机集群甚至显卡中的大量独立处理器上来极大地加速 VM2。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速相关的分子计算，我们相信 VM2 也能做到这一点。公共健康相关性：我们希望让科学家通过计算机程序更快地设计新药。问题在于该程序执行计算所需的时间太长。这个项目是通过改变程序来加快计算速度，使其能够让大量的计算机处理器协同工作，在短时间内计算出答案。