TMPfold: A Web Tool for Predicting Stability of Transmembrane α-Helix Association
TMPfold: A Web Tool for Predicting Stability of Transmembrane α-Helix Association
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DOI：
10.1016/j.jmb.2019.10.024
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发表时间：
2020-05-15
影响因子：
5.6
通讯作者：
Pogozheva, Irina D.
中科院分区：
文献类型：
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作者：
Lomize, Andrei L.;Schnitzer, Kevin A.;Pogozheva, Irina D.
估计跨膜(TM)α-螺旋结合的能量对于理解膜蛋白的折叠和其功能组装的形成是至关重要的。开发了一种新的基于物理的方法，并在TMPold Web服务器上实现，用于计算已知结构的TMα束中TM螺旋缔合自由能(德尔塔G(ASC))。使用36个TM复合体的实验Delta G(ASC)值验证了该方法，其中包括10个血糖素A突变体的二聚体。计算的TM螺旋突变引起的自由能变化(Delta Delta G(ASC))与42个细菌视紫红质突变和25个菱形蛋白酶突变的稳定性的实验变化相关联。应用TMPold对85个七螺旋TM蛋白的554个PDB结构中的Delta G(ASC)进行了评估，并鉴定了稳定的双螺旋折叠中间体。提出的几种多聚蛋白共翻译螺旋组装的试探性路径与其折叠的实验研究一致。(C)2019爱思唯尔有限公司。保留所有权利。
Estimating energies of transmembrane (TM) alpha-helix association is essential for understanding folding of membrane proteins and formation of their functional assemblies. A new physics-based method was developed and implemented in the TMPfold web server for the calculation of the free energy of TM helix association (Delta G(asc)) in TM alpha-bundles of known structure. The method was verified using the experimental Delta G(asc) values for 36 TM complexes, including dimers of 10 glycophorin A mutants. The calculated free energy changes (Delta Delta G(asc)) caused by mutations in TM helices correlated with experimental changes in the stability of 42 mutants of bacteriorhodopsin and 25 mutants of rhomboid protease. TMPfold was applied for evaluation of Delta G(asc) in 554 PDB structures of 85 seven-helical TM proteins and identification of stable two-helical folding intermediates. The proposed tentative paths of cotranslational helix assembly of several polytopic proteins were consistent with experimental studies of their folding. (C) 2019 Elsevier Ltd. All rights reserved.