MATURATION OF ANTIBODY & ANTIGEN INTERACTIONS

泛喹酚细胞色素c氧化还原酶(细胞色素Bc1复合体) 在细菌的电子传输链中起着核心作用， 线粒体和叶绿体，将氧化还原自由能转化为 通过三磷酸腺苷驱动细胞代谢的质子梯度 综合。该络合物催化泛喹酚的氧化。 膜、细胞色素c的还原和细胞色素c的移位 跨膜的质子[97]。所有的Bc1复合体都包含三个 假体基团所结合的基本亚单位：a 细胞色素(Cyt)b与高电势和低电势的血红素bh和bl， 含2Fe2S中心和细胞色素的铁硫蛋白(Isp) C1与另一个亚铁血红素基团。催化机理涉及两个方面 氧化(OO位)或还原(OI位)的催化中心 奎诺内斯。几种线粒体Bc1的晶体结构 结合和不结合抑制物(豆蔻素)的复合体 网站在过去一年中可用[98，99]。在结构中 结合了Statmatellin，部分isp结构域就会发生翻转 在没有抑制剂的情况下恢复到其在结构中的位置[99]。这 表明从Oo位到Cytc1的电子转移路径 涉及到运营商的大量移动。我们的合作者，A.R. Croft，为我们提供了鸡心的晶体结构 线粒体Bc1复合体，结合和不结合抑制物在 Oo站点[99]。对这两种结构的比较表明， 铁硫蛋白(Isp)移动头的旋转轴 旋转角度。我们已经准备了两个系统，包括 两种结构的细胞色素b、细胞色素c1和isp结构域 平衡。我们研究了控制旋转的机制 利用定向分子动力学(SMD)模拟实现的isp磁头 [3-8,100]。在模拟中，外力必须施加到 Isp提供适当的扭矩来诱导旋转。我们 主要感兴趣的是揭示施加的几何约束 关于BC1的其他子单元对ISP头的移动 很复杂。我们将模拟ISP头在 通过SMD诱导细胞色素B和细胞色素C 1亚基的存在 旋转。此模拟将提供以下信息： Isp头的运动不受限制或涉及分子 可能导致或阻止旋转的相互作用。后一种情况 可能表明突变改变了催化反应的速度。

The ubiquinol cytochrome c oxidoreductase (cytochrome bc1 complex) plays a central role in electron transport chains of bacteria, mitochondria and chloroplasts, converting redox free energy into a proton gradient used to drive the cell's metabolism through ATP synthesis. This complex catalyzes the oxidation of ubiquinol in the membrane, the reduction of cytochrome c and the translocation of protons across the membrane [97]. All bc1 complexes contain three essential sub-units to which the prosthetic groups are bound: a cytochrome (cyt) b with high- and low-potential hemes bH and bL, an iron sulfur protein (ISP) containing a 2Fe2S center, and a cytochrome c1 with another heme group. The catalytic mechanism involves two catalytic sites for oxidation (Oo site) or reduction (Oi site) of the quinones. The crystal structures of several mitochondrial bc1 complexes with and without an inhibitor (stigmatellin) bound at the Oo site became available during the past year [98, 99]. In the structure with stigmatellin bound, part of the ISP domain is turned with respect to its position in the structure without the inhibitor [99]. This suggests that the electron transfer path from the Oo site to cyt c1 involves a substantial movement of the ISP. Our collaborator, A. R. Crofts, provided us with crystal structures of chicken heart mitochondria bc1 complexes, with and without the inhibitor bound at the Oo site [99]. Comparison of these two structures revealed the axis of rotation of the iron sulfur protein (ISP) mobile head and the angle of rotation. We have prepared two systems consisting of the cytochrome b, cytochrome c1 and ISP domains of the two structures for equilibration. We investigate the mechanism governing the rotation of the ISP head by means of Steered Molecular Dynamic (SMD) simulations [3-8, 100]. In the simulations, external forces have to be applied to the ISP to provide an appropriate torque inducing the rotation. We are mainly interested in revealing the geometrical constraints imposed on the movement of the ISP head by the other sub-units of the bc1 complex. We will simulate the rotation of the ISP head in the presence of cyt b and cyt c1 sub-units by using SMD to induce the rotation. This simulation will provide the information on whether the motion of the ISP head is unconstrained or it involves molecular interactions that may induce or prevent the rotation. The latter case may indicate mutations that alter the rate of the catalytic reaction.