Protein dynamic communities from elastic network models align closely to the communities defined by molecular dynamics.
Protein dynamic communities from elastic network models align closely to the communities defined by molecular dynamics.
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DOI：
10.1371/journal.pone.0199225
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Jernigan RL
中科院分区：
文献类型：
--
作者：
Mishra SK;Jernigan RL
蛋白质中的动态群落包含单独表现出刚体运动的内聚结构单元。这些可以对应于结构域，但通常是较小的部分，在蛋白质的内部运动中相对于彼此移动，这是其功能动力学的关键。先前的研究强调了理解配体诱导的变构调节本质的重要性。这些研究报告说，关键群落残基的突变可能会阻碍群落之间变构信号的传递。通常使用分子动力学 (MD) 模拟（约 100 纳秒或更长）来识别群落，这对于较大的蛋白质来说是一项艰巨的任务。在本研究中，我们提出从 MD 模拟中获得的动态社区也可以通过更简单的模型——弹性网络模型（ENM）来获得。为了验证这个前提，我们比较了从 MD 和 ENM 获得的 44 种蛋白质的特定群落。我们通过两种方法评估社区中的对应性，并计算用于社区检测的动态互相关数据的一致性程度。我们的研究揭示了 MD 和 ENM 的群落之间存在很强的对应性，并且残差互相关也具有良好的一致性。重要的是，我们观察到 MD 的动态社区可以用 ENM 精确再现。通过 ENM，我们还比较了 T4 溶菌酶稳定和不稳定突变型与其野生型的群落结构。我们发现，与稳定突变体相比，不稳定突变体群落与野生型群落的一致性要差得多，这表明这种基于 ENM 的群落结构可以作为快速识别有害突变体的一种手段。
Dynamic communities in proteins comprise the cohesive structural units that individually exhibit rigid body motions. These can correspond to structural domains, but are usually smaller parts that move with respect to one another in a protein’s internal motions, key to its functional dynamics. Previous studies emphasized their importance to understand the nature of ligand-induced allosteric regulation. These studies reported that mutations to key community residues can hinder transmission of allosteric signals among the communities. Usually molecular dynamic (MD) simulations (~ 100 ns or longer) have been used to identify the communities—a demanding task for larger proteins. In the present study, we propose that dynamic communities obtained from MD simulations can also be obtained alternatively with simpler models–the elastic network models (ENMs). To verify this premise, we compare the specific communities obtained from MD and ENMs for 44 proteins. We evaluate the correspondence in communities from the two methods and compute the extent of agreement in the dynamic cross-correlation data used for community detection. Our study reveals a strong correspondence between the communities from MD and ENM and also good agreement for the residue cross-correlations. Importantly, we observe that the dynamic communities from MD can be closely reproduced with ENMs. With ENMs, we also compare the community structures of stable and unstable mutant forms of T4 Lysozyme with its wild-type. We find that communities for unstable mutants show substantially poorer agreement with the wild-type communities than do stable mutants, suggesting such ENM-based community structures can serve as a means to rapidly identify deleterious mutants.
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影响因子：
5.5
作者：
Calligari, Paolo;Gerolin, Marco;Polimeno, Antonino
通讯作者：
Polimeno, Antonino
影响因子：
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作者：
Guerois, R;Nielsen, JE;Serrano, L
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DOI：
10.1016/s1359-0278(97)00024-2
发表时间：
1997-01-01
期刊：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
3.4
作者：
Atilgan, AR;Durell, SR;Bahar, I
通讯作者：
Bahar, I