EKO Approach To Find Small Molecules That Perturb Protein Protein Interaction

描述(由申请人提供)：制药业的主要新前沿之一是设计小分子来扰乱蛋白质-蛋白质相互作用PPI。许多药物验证的蛋白质靶标都涉及PPI，但总的来说，可用来发现干扰这些靶标的小分子的方法是不够的。小分子PPI模仿有限责任公司拥有知识产权，涵盖了一种创新的设计有机化合物的新方法，可以扰乱PPI。这一方法的核心是两个计算协议。第一种是被称为猝灭分子动力学(QMD)的过程，用于确定小分子的首选构象；第二种是被称为探索键定向(EKO)的专利算法，用于大规模挖掘结构表征的PI。小分子PPI模仿LLC提议通过以下方式产生收入流：(I)确定可用于干扰PPI的可专利化学类型并销售这些信息，或在此基础上进行合作；以及(Ii)准备和测试该公司将拥有的可专利化学类型，然后出售或用于达成合作协议。要开发EKO的商业潜力，有几个步骤是必要的。第一个是开发一个QMD版本，该版本不会因为需要从商业供应商那里许可软件例程而受到阻碍。其次，有必要调整软件，使其能够在用户界面更友好、命令行更少的标准台式计算机上运行得更快。第三，该软件需要用实验数据进一步验证，实验数据表明化合物可以结合这一过程中涉及的PPI。这个应用程序是为了支持这三个领域的努力。

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.