MATURATION OF ANTIBODY & ANTIGEN INTERACTIONS

泛醇细胞色素c氧化还原酶（细胞色素bc1复合物） 在细菌的电子传递链中起着核心作用， 线粒体和叶绿体，将氧化还原自由能转化为 用于通过ATP驱动细胞代谢的质子梯度 合成. 这种复合物催化泛醇在 细胞色素c的还原和 质子穿过膜[97]。 所有的bc1复合物都含有三个 与辅基结合的必需亚单位： 细胞色素（cyt）B与高和低电位血红素bH和bL， 含2Fe2S中心的铁硫蛋白（ISP）和细胞色素 C1与另一个血红素基团。 催化机制涉及两个 用于氧化（Oo位点）或还原（Oi位点）的催化位点 醌类。 几种线粒体bc1的晶体结构 复合物与和不与抑制剂（stigmatellin）结合在Oo 在过去的一年里，网站变得可用[98，99]。 结构中 与stigmatellin结合，ISP域的一部分被转成 在没有抑制剂的情况下，其在结构中的位置[99]。 这 表明从Oo位点到cyt c1的电子转移路径 涉及ISP的实质性移动。 我们的合作者A. R. Crofts，为我们提供了鸡心的晶体结构 线粒体bc1复合物，有和没有抑制剂结合在 [99]第99话 这两种结构的比较揭示了 铁硫蛋白（ISP）移动的头和 旋转角 我们准备了两个系统， 两种结构的细胞色素B、细胞色素c1和ISP结构域， 平衡 我们调查的机制，管理的旋转 ISP头通过操纵分子动力学（SMD）模拟 [3-8，100]。 在模拟中，必须施加外力， ISP以提供引起旋转的适当扭矩。 我们 主要感兴趣的是揭示几何约束 由bc1的其他子单元移动ISP头 复杂. 我们将模拟ISP头在 细胞色素B和细胞色素c1亚单位的存在，通过使用SMD诱导 旋转 该模拟将提供关于是否 ISP头的运动不受约束，或者涉及分子 可能引起或阻止旋转的相互作用。 后一种情况 可能表明改变催化反应速率的突变。

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.