EKO Approach To Find Small Molecules That Perturb Protein Protein Interaction

描述（由申请人提供）：制药行业的主要新领域之一是设计干扰蛋白质-蛋白质相互作用 PPI 的小分子。许多经过医学验证的蛋白质靶点都涉及质子泵抑制剂（PPI），但总的来说，发现干扰这些蛋白质的小分子的方法还不够充分。 Small Molecule PPI Mimics LLC 拥有知识产权，涵盖一种创新的新方法来设计可干扰 PPI 的有机化合物。两个计算协议是该方法的核心。第一个是称为淬灭分子动力学 (QMD) 的程序，用于确定小分子的首选构象；第二个是称为探索关键方向 (EKO) 的专有算法，用于大规模数据挖掘结构特征 PPI。 Small Molecule PPI Mimics LLC 提议通过以下方式产生收入流：(i) 识别可用于干扰 PPI 的可专利化学型并出售此信息，或基于此进行合作； (ii) 准备和测试公司将拥有的可专利化学型，然后出售或用于签订合作协议。开发 EKO 的商业潜力需要采取几个步骤。第一个是开发 QMD 版本，该版本无需从商业供应商处获得软件例程许可。其次，有必要对软件进行调整，使其能够在标准台式计算机上运行得更快，并具有更用户友好的界面和更少的命令行。第三，该软件需要用实验数据进一步验证，表明化合物可以结合该过程中涉及的质子泵抑制剂。该应用程序旨在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.