Multilevel Parallelization of Software for Accurate Protein-Ligand Affinities

描述（由申请人提供）：许多药物是通过与特定蛋白质结合从而阻断或改变其作用的小分子。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位点并阻止其帮助制造新病毒而起作用。当科学家确定一种蛋白质，如HIV蛋白酶，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。这种结构为化学家设计一种能紧密结合蛋白质的小分子提供了有价值的指导。然而，即使他们知道蛋白质的结构，在设计药物时仍然有很多试验和错误。许多研究人员已经开发了计算机程序来帮助预测一个给定的分子是否会结合一个给定的蛋白质，但没有太多成功。现在，VeraChem在过去几年中开发的新软件为这个问题提供了非常好的结果。然而，该软件需要很长的时间来运行，如果它更快的话会更有用。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。他们可以检查一种化合物是否能对抗他们的蛋白质，并继续对抗蛋白质的突变形式，从而避免耐药性。因此，VM2的快速版本将是非常有用的，并且将是有价值的商业产品。加速VeraChem的方法VM2并不像在更快的计算机上运行它那么简单，因为近年来单个计算机的速度并没有提高多少。然而，正在发生变化的是，计算机正在使用越来越多的处理器。该项目的目标是通过将其计算工作分散在单个计算机、计算机集群甚至视频卡中的大量独立处理器上来极大地加速VM2。这不是一个简单的任务，但研究人员已经能够以这种方式加快相关的分子计算，我们相信VM2也可以做到这一点。 公共卫生相关性：我们希望让科学家用计算机程序更快地设计新药。问题是这个程序需要太长的时间来进行计算。这个项目是通过改变程序来加快计算速度，使它可以使大量的计算机处理器协同工作，在短时间内计算出答案。

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.