Membrane protein structure in lipido: computational developments.

描述（由申请人提供）：脂质膜蛋白结构：计算发展。本申请是为了响应膜蛋白结构生物学项目公告PA-10-228。该项目的总体目标是开发新的计算方法，在磷脂双层膜的功能环境中对完整膜蛋白进行核磁共振结构分析。这些蛋白质/脂质大分子复合物可以用核磁共振光谱进行表征。生物分子核磁共振实验方面（样品制备、仪器、脉冲序列）达到先进水平；然而，计算方法比较落后。我们建议通过三个具体目标来缩小这一技术差距，旨在促进结构确定和提高结构质量。为了方便结构确定和扩大我们工作的影响，我们的方法将与广泛使用的核磁共振结构细化程序相结合，通过限制分子动力学和从头开始的蛋白质结构预测。为了最大限度地提高结构质量和信息含量，我们的方法将根据实验数据提供的膜特异性结构约束进行定制。

DESCRIPTION (provided by applicant): Membrane protein structure in lipido: computational developments. This application is in response to Program Announcement PA-10-228 for Structural Biology of Membrane Proteins. The overall goal of the project is to develop new computational methods for NMR structural analysis of integral membrane proteins within their functional environment of the phospholipid bilayer membrane. These protein/lipid macromolecular complexes can be characterized using NMR spectroscopy. The experimental aspects of biomolecular NMR (sample preparation, instrumentation, pulse sequences) have reached an advanced level; however, computational methods are lagging behind. We propose to close this technology gap with three specific aims designed to facilitate structure determination and increase structural quality. To facilitate structure determination and broaden the impact of our work, our methods will be integrated with widely used programs for NMR structure refinement by restrained molecular dynamics and de novo protein structure prediction. To maximize the structural quality and information content, our methods will be tailored for the membrane-specific structural restraints provided by the experimental data.