Calculating Ensemble Averaged Descriptions of Protein Rigidity without Sampling
Calculating Ensemble Averaged Descriptions of Protein Rigidity without Sampling
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DOI：
10.1371/journal.pone.0029176
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发表时间：
2012-02-22
期刊：
影响因子：
3.7
通讯作者：
Jacobs, Donald J.
中科院分区：
文献类型：
--
作者：
Gonzalez, Luis C.;Wang, Hui;Jacobs, Donald J.
先前的研究表明，蛋白质的刚性与热力学稳定性有关，特别是在有利于形成天然结构的条件下。采用整体棒卵石博弈算法，有效地计算了单一构象的机械网络刚度特性。然而，热力学性质需要对来自可接近构象集合的许多样本进行平均，以准确地解释网络拓扑结构的波动。我们开发了一个平均场虚拟卵石游戏（VPG），它通过一个单一的有效网络来表示网络的集合。也就是说，可以在一对刚体之间形成的所有可能的距离约束（或杆）的数量被平均数量所取代。由此产生的有效网络被视为具有加权边，其中边的权重量化了其吸收自由度的能力。在这个有效的网络上，VPG被解释为一个流问题，从而消除了采样的需要。在272个蛋白质结构的非冗余数据集中，我们首次将VPG应用于蛋白质。我们的结果从数值和视觉上表明，VPG的刚度表征准确地反映了棒上的系综平均（PG）性能。这一结果将VPG定位为理解化学相互作用在维持蛋白质稳定性中所起的机械作用的有效替代方法。
Previous works have demonstrated that protein rigidity is related to thermodynamic stability, especially under conditions that favor formation of native structure. Mechanical network rigidity properties of a single conformation are efficiently calculated using the integer body-bar Pebble Game (PG) algorithm. However, thermodynamic properties require averaging over many samples from the ensemble of accessible conformations to accurately account for fluctuations in network topology. We have developed a mean field Virtual Pebble Game (VPG) that represents the ensemble of networks by a single effective network. That is, all possible number of distance constraints (or bars) that can form between a pair of rigid bodies is replaced by the average number. The resulting effective network is viewed as having weighted edges, where the weight of an edge quantifies its capacity to absorb degrees of freedom. The VPG is interpreted as a flow problem on this effective network, which eliminates the need to sample. Across a nonredundant dataset of 272 protein structures, we apply the VPG to proteins for the first time. Our results show numerically and visually that the rigidity characterizations of the VPG accurately reflect the ensemble averaged (PG) over bar properties. This result positions the VPG as an efficient alternative to understand the mechanical role that chemical interactions play in maintaining protein stability.