Kinetics analysis methods for approximate folding landscapes.
Kinetics analysis methods for approximate folding landscapes.
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近似折叠景观的动力学分析方法。
DOI：
10.1093/bioinformatics/btm199
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发表时间：
2007
期刊：
影响因子：
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通讯作者：
Amato,NancyM
中科院分区：
文献类型：
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作者：
Tapia,Lydia;Tang,Xinyu;Thomas,Shawna;Amato,NancyM
动机：蛋白质运动在许多生化过程中起着重要作用。实验室研究通常根据它们的动力学来量化这些运动，比如蛋白质折叠的速度或某些有趣状态的数量，比如自然状态。动力学指标提供了折叠过程的可量化测量，可以在一组蛋白质（如野生型蛋白质及其突变体）之间进行比较。结果：我们提出了两种新技术，基于地图的主方程解和基于地图的蒙特卡罗模拟，通过折叠率和群体动力学从近似折叠景观（称为地图的模型）来研究蛋白质动力学。从这两种新技术中，也可以研究描述折叠过程的有趣度量，例如反应坐标。在本文中，我们着重于两个指标，形成螺旋和结构形成周围的色氨酸残基。这两个指标通常在实验室中分别通过圆二色性（CD）光谱分析和色氨酸荧光实验来研究。我们在这里使用的近似景观模型是我们之前提出并验证的蛋白质构象及其相关转变的地图。与传统的主方程和蒙特卡罗模拟等方法相比，我们的技术既快速又易于计算全长详细的蛋白质模型。我们通过比较折叠率和已知的实验结果来验证我们的基于图的动力学技术。我们还深入研究了各种蛋白质在色氨酸残基附近的种群动力学、螺旋形成和结构。可用性：我们邀请社区通过提交到我们的服务器：http://parasol.tamu.edu/foldingserver/Contact:amato@cs.tamu.edu来帮助我们丰富我们公开可用的运动和动力学分析数据库
Motivation:Protein motions play an essential role in many biochemical processes. Lab studies often quantify these motions in terms of their kinetics such as the speed at which a protein folds or the population of certain interesting states like the native state. Kinetic metrics give quantifiable measurements of the folding process that can be compared across a group of proteins such as a wild-type protein and its mutants.Results:We present two new techniques, map-based master equation solution and map-based Monte Carlo simulation, to study protein kinetics through folding rates and population kinetics from approximate folding landscapes, models called maps. From these two new techniques, interesting metrics that describe the folding process, such as reaction coordinates, can also be studied. In this article we focus on two metrics, formation of helices and structure formation around tryptophan residues. These two metrics are often studied in the lab through circular dichroism (CD) spectra analysis and tryptophan fluorescence experiments, respectively. The approximated landscape models we use here are the maps of protein conformations and their associated transitions that we have presented and validated previously.In contrast to other methods such as the traditional master equation and Monte Carlo simulation, our techniques are both fast and can easily be computed for full-length detailed protein models. We validate our map-based kinetics techniques by comparing folding rates to known experimental results. We also look in depth at the population kinetics, helix formation and structure near tryptophan residues for a variety of proteins.Availability:We invite the community to help us enrich our publicly available database of motions and kinetics analysis by submitting to our server: http://parasol.tamu.edu/foldingserver/Contact:amato@cs.tamu.edu