Multilevel Parallelization of Software for Accurate Protein-Ligand Affinities

描述（由申请人提供）：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蛋白酶抑制剂是一种重要的艾滋病治疗方法，它通过结合蛋白酶的活性位点并阻止它帮助制造新病毒而起作用。当科学家们确定一种蛋白质，如HIV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。这种结构为化学家们设计一种能将蛋白质紧密结合的小分子提供了有价值的指导。然而，即使他们知道了蛋白质的结构，在设计药物的过程中仍然有很多的试验和错误。许多研究人员已经在计算机程序上工作，以帮助预测一个给定的分子是否会与一个给定的蛋白质结合，但没有多少成功。现在，VeraChem在过去几年里开发的新软件对这个问题给出了非常好的结果。然而，该软件需要很长时间才能运行，如果速度快得多，将会有用得多。例如，如果化学家对一种新化合物有了一个想法，他们可以在几分钟内得到答案，而不是几天。他们可以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他们的蛋白质起作用的化合物是否能继续对突变形式的蛋白质起作用，从而避免抗药性。因此，快速版本的VM2将非常有用，并且将是一个有价值的商业产品。加快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，正在发生变化的是，计算机的处理器越来越多。这个项目的目标是通过将VM2的计算工作分散到单个计算机、计算机集群甚至视频卡中的大量独立处理器上，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以这种方式加速相关的分子计算，我们有信心同样可以为VM2完成。

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.