SBIR Phase I: Software for High-Throughput Combinatorial Design and Curation of Novel Proteins

这个小企业创新研究（SBIR）项目的更广泛的影响/商业潜力是使科学家能够使用高通量蛋白质工程设计蛋白质结构，通过从DNA合成器中轻松经济地购买这些蛋白质的合成DNA编码，获得特定实验所需的确切生物工具。目前，研究人员在他们的实验中使用蛋白质作为生物工具，花费了大量的时间、精力和金钱来设计和人工构建这些蛋白质，而且成本太高，以至于研究人员满足于使用一种不太适合他们实验目的的工具。确保实验具有广泛的生物学适用性，需要正确的控制，包括积极的和消极的，以及必须验证的多种询问策略。如果不满足这些要求，实验的适用性可能会比预期的要窄。在今天的实验环境中，蛋白质被用作生物工具，存在技术障碍，使广泛的适用性难以实现。该提案旨在通过使科学家能够设计和经济地获得一套逻辑完整的蛋白质工具，从而使他们能够在逻辑上优化他们的实验，从而减少这些技术障碍。此外，通过对这些设计进行功能性注释，科学家将能够迅速将这些细节传播给其他科学家。这个SBIR一期项目建议为科学家开发软件来设计和管理新蛋白质的组合文库，以便DNA可以直接从DNA合成公司订购。该软件的目的是使科学家能够设计和购买一套逻辑完整的蛋白质，以促进其实验的广泛生物学适用性。今天，合成DNA供应商正在发展以经济的价格制造DNA序列组合文库的能力。然而，目前还没有有效的方法来设计这样一个用于制造的库，使DNA合成器的能力与蛋白质工程师的实验要求相匹配。该软件旨在将科学家的设计结构为氨基酸产品的计算复杂配方，这些氨基酸产品可以以与其制造能力相匹配的方式表达到DNA合成器中。该软件将遵循计算规则，从成分配方中生成生物学上合理的蛋白质。然后，它将结果数据传输到DNA合成器。此外，它将为研究人员提供一个简单的用户界面来评估和指定生成的蛋白质的功能，以便其他人可以从他们的设计中学习。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to enable scientists to design protein constructs using high throughput protein engineering to obtain the exact biological tools they need for a particular experiment by purchasing synthetic DNA coding for these proteins from a DNA synthesizer easily and economically. Currently, researchers using proteins as biological tools in their experiments expend significant time, effort and money to design and manually build these proteins - and too often that cost is so high that researchers settle for using a tool that is less than optimal for their experimental purposes. Ensuring broad biological applicability of an experiment requires correct controls, both positive and negative, as well as multiple interrogation strategies that must each be validated. Without satisfying these requirements, an experiment's applicability may be narrower than desired. In today's experimental landscape where proteins are used as biological tools, there are technical hurdles that make broad applicability difficult to achieve. This proposal aims to reduce these technical barriers by enabling scientists to design and economically obtain a logically complete set of protein tools in a way that allows them to logically optimize their experiments. Further, by functionally annotating these designs, a scientist will be able to rapidly disseminate those details to other scientists.This SBIR Phase I project proposes to develop software for scientists to design and curate combinatorial libraries of novel proteins so that DNA can be directly ordered from DNA synthesis companies. The purpose of this software is to enable a scientist to design and purchase a logically complete set of proteins that promotes the broad biological applicability of their experiment. Today, synthetic DNA suppliers are developing the ability to manufacture combinatorial libraries of DNA sequences at economical prices. However, there is currently no efficient means to design such a library for manufacture that matches the DNA synthesizers' capabilities with a protein engineer's experimental requirements. This software aims to structure the scientist's designs as a computationally complex recipe for amino acid products that can be expressed to a DNA synthesizer in a way that matches their manufacturing capabilities. This software will follow computational rules for generating biologically reasonable proteins from a recipe of components. It will then transmit the resulting data to DNA synthesizers. In addition, it will provide a straightforward user-interface for researchers to evaluate and designate the functionality of the generated proteins so that others may learn from their designs.