EKO Approach To Find Small Molecules That Perturb Protein Protein Interaction

描述（由申请人提供）：制药行业的主要新前沿之一是设计小分子干扰蛋白质-蛋白质相互作用PPI。许多经医学验证的蛋白质靶点涉及PPI，但发现干扰这些靶点的小分子的方法总体上是不够的。Small Molecule PPI Mimics LLC拥有知识产权，涵盖了设计可干扰PPI的有机化合物的创新方法。两个计算协议是这种方法的核心。第一个是一种名为猝灭分子动力学（QMD）的程序，用于确定小分子的首选构象，第二个是一种名为探索关键方向（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建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;以及（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。第一个是开发一个不受商业供应商许可软件例程的限制的QMD版本。第二，有必要调整软件，使其能够在标准台式计算机上运行得更快，界面更友好，命令行更少。第三，需要用实验数据进一步验证该软件，这些数据表明化合物可以结合这一过程中涉及的PPI。本申请旨在支持这三个领域的工作。

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.