SBIR Phase I: Nanoengineered Epitaxial Surfaces for High Throughput Protein Crystallization

这个小型企业创新研究(SBIR)第一阶段项目建议开发一种新型的纳米工程表面来外延成核蛋白质晶体。这些表面应该会极大地加速大多数高通量结构基因组学的努力。外延表面的基本概念是制备具有与蛋白质单位细胞的大小和周期相称的化学调制的表面。推测蛋白质生长溶液暴露在非均相核试剂表面的某些组成周期(5-100 nm)下，可以诱导形成有序的吸附蛋白质分子层，从而形成蛋白质晶体的初始核。由于对于给定的未知蛋白质，单位细胞事先是未知的，所以以基于芯片的格式将多相核酸库制备为组合文库，每单位芯片面积具有多种调制。在这个第一阶段的提案中，将开发方法和技术，以便能够更有效地调查表面和蛋白质，目的是更好地确定表面在诱导核形成中的作用。该项目的商业应用是在生物研究和药物发现和开发领域。

This Small Business Innovation Research (SBIR) Phase I project proposes to develop a new type ofnanoengineered surface to epitaxially nucleate protein crystals. These surfaces should greatly accelerate most high throughput Structural Genomics efforts. The basic concept for the epitaxial surfaces is to prepare a surface that possesses chemical modulations commensurate in size and periodicity to protein unit cells. It is speculated that exposure of the protein growth solution to certain compositional periodicities (5-100 nm) on the surface of the heterogeneous nucleants induces an ordered layer of sorbed protein molecules which form the incipient nucleus of the protein crystal. Since for a given unknown protein the unit cell is not known in advance, the heterogeneous nucleants are prepared as a combinatorial library in a chip based format, with a wide variety of modulations per unit chip area. In this Phase I proposal, methods and techniques will be developed to allow a more efficient survey of surfaces and proteins with the goal of better defining the role of the surfaces in inducing nucleation.The commercial applications of this project are in the area of biological research and in drug discovery and development.