Calculation of proton transfers in Bacteriorhodopsin bR and M intermediates.
Calculation of proton transfers in Bacteriorhodopsin bR and M intermediates.
复制标题
计算细菌视紫红质 bR 和 M 中间体中的质子转移。
DOI：
10.1021/bi034482d
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Gunner,MR
中科院分区：
文献类型：
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作者：
Song,Yifan;Mao,Junjun;Gunner,MR
用多构象连续静电法计算了细菌视紫红质在bR、早期M和晚期M状态下的9种晶体结构的残余电离态。这结合了连续静电和分子力学，推导出电离态和极性残基和水的位置的平衡分布。三个中心簇群[视网膜席夫碱（SB），天冬氨酸85和天冬氨酸212]在bR结构电离，而质子已从SB+转移到天冬氨酸85-在后期M结构匹配的实验结果。M中的质子移动是由于较弱的SB+-离子化酸和更有利的SB 0-离子化酸相互作用后，视网膜异构化。质子释放簇（Glu 194和Glu 204）结合bR中的一个质子，其在后期M中通过pH 8失去到水中。在bR中，半电离态通过电荷-偶极相互作用而稳定，而完全电离则被紧密排列的酸之间的电荷-电荷排斥所禁止。在M中，酸分开，允许完全电离。Arg 82运动连接中心和质子释放簇中的质子移动。两个簇的总电荷的变化通过直接的长程相互作用耦合。单独计算考虑内腔中的连续或显式水。明确的沃茨和附近的极性残基可以重新定向，以稳定不同的电荷分布。在这些计算中，质子释放到蛋白质的低pH胞外侧，其中残留物电离与介质保持平衡。因此，区分中间体的关键变化确实被困在结构中。
Residue ionization states were calculated in nine crystal structures of bacteriorhodopsin trapped in bR, early M, and late M states by multiconformation continuum electrostatics. This combines continuum electrostatics and molecular mechanics, deriving equilibrium distributions of ionization states and polar residue and water positions. The three central cluster groups [retinal Schiff base (SB), Asp 85 and Asp 212] are ionized in bR structures while a proton has transferred from SB+to Asp 85-in late M structures matching experimental results. The proton shift in M is due to weaker SB+-ionized acid and more favorable SB0-ionized acid interactions following retinal isomerization. The proton release cluster (Glu 194 and Glu 204) binds one proton in bR, which is lost to water by pH 8 in late M. In bR the half-ionized state is stabilized by charge−dipole interactions while full ionization is disallowed by charge−charge repulsion between the closely spaced acids. In M the acids move apart, permitting full ionization. Arg 82 movement connects the proton shifts in the central and proton release clusters. Changes in total charge of the two clusters are coupled by direct long-range interactions. Separate calculations consider continuum or explicit water in internal cavities. The explicit waters and nearby polar residues can reorient to stabilize different charge distributions. Proton release to the low-pH, extracellular side of the protein occurs in these calculations where residue ionization remains at equilibrium with the medium. Thus, the key changes distinguishing the intermediates are indeed trapped in the structures.