Accessing gap-junction channel structure-function relationships through molecular modeling and simulations.
Accessing gap-junction channel structure-function relationships through molecular modeling and simulations.
复制标题
通过分子建模和仿真访问间隙结构结构功能关系。
DOI：
10.1186/s12860-016-0121-9
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发表时间：
2017-01-17
期刊：
影响因子：
--
通讯作者：
Perez-Acle T
中科院分区：
文献类型：
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作者：
Villanelo F;Escalona Y;Pareja-Barrueto C;Garate JA;Skerrett IM;Perez-Acle T
缝隙连接通道（GJC）是连接相邻细胞胞质的蛋白质通道。这些通道允许高达约1 kDa的分子（包括水、离子和其他代谢物）在细胞间转移。揭示编码到这些通道的分子结构中的结构-功能关系对于深入了解其广泛的生物学功能包括电突触、炎症、发育和组织稳态是必要的。从早期的工作，计算方法一直是至关重要的分析和解释实验观察。随着晶体学结构的出现，分子建模和模拟已成为评估GJC结构-功能关系的重要工具。不同的连接蛋白异构体建模，模拟运输过程，并探索分子变异，提供了新的假设和开箱即用的方法来研究这些重要的通道。在这里，我们回顾了基础结构的研究和最近的发展GJC使用分子建模和模拟技术，突出的方法和实验证据的串扰。通过比较分子建模和模拟技术获得的结果与结构和功能的信息，从最近的文献和结构数据库，我们提供了一个关键的评估的结构-功能的关系，可以从理论和实验证据之间的交界处获得。
Gap junction channels (GJCs) are massive protein channels connecting the cytoplasm of adjacent cells. These channels allow intercellular transfer of molecules up to ~1 kDa, including water, ions and other metabolites. Unveiling structure-function relationships coded into the molecular architecture of these channels is necessary to gain insight on their vast biological function including electrical synapse, inflammation, development and tissular homeostasis. From early works, computational methods have been critical to analyze and interpret experimental observations. Upon the availability of crystallographic structures, molecular modeling and simulations have become a valuable tool to assess structure-function relationships in GJCs. Modeling different connexin isoforms, simulating the transport process, and exploring molecular variants, have provided new hypotheses and out-of-the-box approaches to the study of these important channels. Here, we review foundational structural studies and recent developments on GJCs using molecular modeling and simulation techniques, highlighting the methods and the cross-talk with experimental evidence. By comparing results obtained by molecular modeling and simulations techniques with structural and functional information obtained from both recent literature and structural databases, we provide a critical assesment of structure-function relationships that can be obtained from the junction between theoretical and experimental evidence.