EKO Approach To Find Small Molecules That Perturb Protein Protein Interaction

EKO 方法寻找干扰蛋白质相互作用的小分子

基本信息

批准号：
8714576
负责人：
KEVIN BURGESS
金额：
$ 22.48万
依托单位：
SMALL MOLECULE PPI MIMICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-05 至 2016-06-04
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8714576
关键词：
Address Agreement Algorithms Amino Acids Area Binding Binding Proteins Bioinformatics Budgets Cellular biology Code Collaborations Computer software Computers Copyright Data Development Dimerization Drug Industry Effectiveness Generations HIV-1 Heart Housing Intellectual Property Investments Legal patent Licensing Malignant Neoplasms Marketing Methods Mining Molecular Conformation Outcome Peptide Hydrolases Pharmaceutical Chemistry Pharmacologic Substance Phase Procedures Process Proteins Protocols documentation Publishing Resources Running Sampling Series Side Simulate Staging Stream Techniques Testing Texas Universities Validation Vendor base caspase-8 commercial application commercialization conformer data mining design drug discovery frontier high throughput screening innovation insight interest molecular dynamics nervous system disorder novel strategies protein protein interaction public health relevance scaffold small molecule therapeutic target tool user-friendly wasting

项目摘要

DESCRIPTION (provided by applicant): One of the major new frontiers in the pharmaceutical industry is the design of small molecules to perturb protein-protein interactions PPIs. Many medicinally validated protein targets involve PPIs, but the methods available to discover small molecules that perturb these are, on aggregate, inadequate. Small Molecule PPI Mimics LLC owns intellectual property covering an innovative new approach to designing organic compounds that can perturb PPIs. Two computational protocols are at the core of this approach. The first is a procedure called Quenched Molecular Dynamics (QMD) to determine preferred conformations of small molecules, and the second is a proprietary algorithm called Exploring Key Orientations (EKO) to data-mine structurally characterized PPIs on a massive scale. Small Molecule PPI Mimics LLC proposes to generate revenue streams by: (i) identifying patentable chemotypes that can be used to interfere with PPIs and selling this information, or entering into collaborations based on it; and, (ii) preparing and testing patentable chemotypes that the company will own, then sell or use to enter into collaborative agreements. Several steps are necessary to exploit the commercial potential of EKO. The first is to develop a version of QMD that is unencumbered by the need to license software routines from commercial vendors. Secondly, it is necessary to adapt the software so that it can be run faster, on a standard desktop computer with a more user-friendly interface with less command lines. Third, that software needs to be further validated with experimental data showing compounds can bind PPIs implicated in this process. This application is to support efforts in these three areas.

描述（由申请人提供）：制药行业的主要新领域之一是小分子以扰动蛋白质 - 蛋白质相互作用的设计。许多有药物验证的蛋白质靶标涉及PPI，但是可用于发现扰动这些分子的小分子的方法不足。小分子PPI Mimics LLC拥有知识产权，涵盖了一种创新的新方法，用于设计可以扰动PPI的有机化合物。两种计算协议是这种方法的核心。第一个是一种称为淬灭分子动力学（QMD）的程序，以确定小分子的首选构象，第二个是一种称为探索关键取向（EKO）的专有算法，以大规模的尺度上具有结构性的PPI。小分子PPI Mimics LLC建议通过以下方式生成收入流：（i）确定可用于干扰PPI并出售此信息或基于IT进行协作的可专利化学型；（ii）准备和测试公司将拥有的可专利化学型，然后出售或使用以签订协作协议。需要几个步骤来利用EKO的商业潜力。首先是开发一个QMD版本，该版本不受商业供应商的软件例程的许可。其次，有必要调整软件，以便可以在具有更少用户友好型命令行的标准台式计算机上运行速度更快。第三，需要通过实验数据进一步验证该软件，显示化合物可以结合与此过程有关的PPI。该申请是为了支持这三个领域的努力。