Supunyabut Chirayut, Fuklang Sunit, Sompornpisut Pornthep
Computational Chemistry Unit Cell, Department of Chemistry, Faculty of Science, Chulalongkorn University, 254 Phayathai Rd. Prathumwan, Bangkok 10330, Thailand.
Computational Chemistry Unit Cell, Department of Chemistry, Faculty of Science, Chulalongkorn University, 254 Phayathai Rd. Prathumwan, Bangkok 10330, Thailand.
J Mol Graph Model. 2015 Jun;59:81-91. doi: 10.1016/j.jmgm.2015.04.003. Epub 2015 Apr 14.
Orientations of proteins in the membranes are crucial to their function and stability. Unfortunately the exact positions of these proteins in the lipid bilayer are mostly undetermined. Here, the spatial orientation of membrane proteins within the lipid membrane was evaluated using a Poisson-Boltzmann solvent continuum approach to calculate the electrostatic free energy of the protein solvation at various orientations in an implicit bilayer. The solvation energy was obtained by computing the difference in electrostatic energies of the protein in water and in lipid/water environments, treating each as an implicit solvent model. The optimal position of transmembrane proteins (TMP) in a lipid bilayer is identified by the minimum in the "downhill" pathway of the solvation energy landscape. The energy landscape pattern was considerably conserved in various TMP classes. Evaluation of the position of 1060 membrane proteins from the orientations of proteins in membranes (OPM) database revealed that most of the polytopic and β-barrel proteins were in good agreement with those of the OPM database. The study provides a useful scheme for estimating the membrane solvation energy made by lipid-exposed amino acids in membrane proteins. In addition, our results tested with the bacterial potassium channel model demonstrated the potential usefulness of the approach in assessing the quality of membrane protein models. The present approach should be applicable for constructing transmembrane proteins-lipid configuration suitable for membrane protein simulations and will have utility for the structural modeling of membrane proteins.
蛋白质在膜中的取向对其功能和稳定性至关重要。不幸的是，这些蛋白质在脂质双层中的精确位置大多尚未确定。在此，利用泊松-玻尔兹曼溶剂连续介质方法评估脂质膜内膜蛋白的空间取向，以计算蛋白质在隐式双层中不同取向时的溶剂化静电自由能。通过计算蛋白质在水和脂质/水环境中的静电能之差来获得溶剂化能，将每一种环境都视为隐式溶剂模型。跨膜蛋白（TMP）在脂质双层中的最佳位置通过溶剂化能景观“下坡”路径中的最小值来确定。能量景观模式在各种TMP类别中相当保守。从膜中蛋白质取向（OPM）数据库评估1060种膜蛋白的位置，结果表明大多数多结构域蛋白和β桶状蛋白与OPM数据库中的结果一致。该研究提供了一种有用的方案，用于估计膜蛋白中脂质暴露氨基酸产生的膜溶剂化能。此外，我们用细菌钾通道模型进行的测试结果证明了该方法在评估膜蛋白模型质量方面的潜在用途。本方法应适用于构建适合膜蛋白模拟的跨膜蛋白-脂质构型，并且对膜蛋白的结构建模具有实用性。
