TriadWeb: An easy-to-use web-based platform for protein engineering.

描述(申请人提供)：单抗和其他基于蛋白质的疗法代表着一个1000多亿美元的不断增长的市场，在癌症、代谢性疾病和其他人类疾病的治疗中有着广泛的应用。因此，任何有助于发现有用蛋白质变体的技术都将对生物学和医学产生重大影响；应用领域包括药物发现、小分子筛选和新诊断和试剂的开发。计算蛋白质设计(CPD)是一种在过去十年中一直处于积极发展中的使能技术。目前的CPD平台高度灵活、功能强大，能够执行广泛的功能。然而，这些平台也很复杂，很难使用，需要大量的知识才能有效地使用。此外，它们需要专门的软件和硬件系统，这给非专家用户的安装和维护带来了很大的技术负担。所有这些因素使得CPD不太可能成为想要设计新蛋白质的实验者的标准工具。为了让实验室科学家能够接触到CPD，Protabit将开发一个基于网络的、易于使用的蛋白质工程商业平台，称为TriadWeb。这个基于网络的平台将建立在Protabit现有的蛋白质工程软件套件Triad的基础上，该套件是与加州理工学院和孟山都公司合作开发的。该项目第一阶段的目标是：(1)开发一套基于网络的“应用程序”，以简单、易于理解的方式充分利用CPD的全部功能；(2)开发后端软件基础设施，以实现基于云的、具有用户身份验证和加密的网络服务；(3)将TriadWeb与安全的、用户分区的数据服务器相结合，以协助组织、共享和查询项目数据；以及(4)结合动态、交互的可视化工具，以帮助查看和解释数据和结果。有了TriadWeb，网络浏览器将收集建议新蛋白质序列文库所需的最少必要输入，然后可以在实验室表达和分析所需的特性。这一投入将使用替补科学家容易理解的概念来收集。TriadWeb将把这些高级指令转换成复杂的蛋白质设计模拟，所有这些都运行在由Protabit维护的专门硬件上或在云环境中。在可能的情况下，结果将以3D分子效果图、图表和图表的形式直观地提供给实验台科学家。幸运的是，CPD领域已经发展到可以将许多CPD功能打包为“应用程序”的地步，其方式与智能手机和iPad上常见的应用程序大致相同。这项第一阶段提案和后续第二阶段提案的总体目标是为实验台科学家提供一套可用的“应用程序”，将复杂的CPD功能转换为简单易学的程序。

DESCRIPTION (provided by applicant): Monoclonal antibodies and other protein-based therapeutics represent a $100+ billion and growing market with broad applications in the treatment of cancer, metabolic diseases, and other human disorders. Thus, any technology that facilitates the discovery of useful protein variants will have a major impact in biology and medicine; application areas include drug discovery, small molecule screening, and the development of new diagnostics and reagents. One such enabling technology that has been under active development in the last decade is computational protein design (CPD). Current CPD platforms are highly flexible, powerful, and capable of performing a wide range of functions. However, these platforms are also complicated and difficult to use, requiring significant knowledge to be wielded effectively. In addition, they require specialized software and hardware systems, which places a high technical burden on installation and maintenance for non-expert users. All these factors make it unlikely that CPD will become a standard tool for experimentalists who want to engineer novel proteins. In order to make CPD accessible to bench scientists, Protabit will develop a web-based, easy-to-use, commercial platform for protein engineering called TriadWeb. This web-based platform will build on Triad, Protabit's existing software suite for protein engineering, which was developed in collaboration with Caltech and Monsanto. The objectives of this Phase I project are: (1) develop a suite of web-based "apps" that harness the full power of CPD in a simple, easy-to-understand way; (2) develop the back-end software infrastructure to enable a cloud-based web-service with user authentication and encryption; (3) couple TriadWeb with a secure, user-partitioned dataserver to assist in the organization, sharing, and querying of project data; and (4) incorporate dynamic, interactive visualization tools to assist in viewing and interpreting data and results. With TriadWeb, the web browser will gather the minimal necessary input needed to suggest new protein sequence libraries that can then be expressed and assayed in the lab for desired properties. This input will be gathered using concepts readily understandable to bench scientists. TriadWeb will convert these high level directives into complex protein design simulations, all running on specialized hardware maintained either by Protabit or in a cloud environment. The results will be provided visually to the bench scientist in the form of 3D molecular renderings, charts and graphs where possible. Fortunately, the field of CPD has advanced to the point where many CPD functions can be packaged as "applications" in much the same manner as the applications that are routinely found on smart phones and iPads. The overall objective of this Phase I proposal and the follow-on Phase II proposal is to provide bench scientists with a usable suite of "apps" that translate complex CPD functions into simple easy-to-learn procedures.