Kinetics of association of anti-lysozyme monoclonal antibody D44.1 and hen-egg lysozyme
Kinetics of association of anti-lysozyme monoclonal antibody D44.1 and hen-egg lysozyme
复制标题
DOI：
10.1016/s0006-3495(00)76532-5
复制
发表时间：
2000-12-01
影响因子：
3.4
通讯作者：
Subramaniam, S
中科院分区：
文献类型：
--
作者：
Altobelli, G;Subramaniam, S
结合速率常数的抗原/抗体协会已计算的布朗动力学模拟D。L. Ermak和J.A. McCammon，J. Chem. Phys. 69：1352-1360，1978。单克隆抗体（mAb）D44.1的模型基于晶体学数据（B. C. Braden等人，J. Mol. Biol 243：767-781，1994）。将抗原导向抗体结合位点的静电力通过求解线性化的泊松-玻尔兹曼方程来计算。D44.1-HEL复合物显示与相关抗溶菌酶抗体HyHEL-5-HEL系统非常相似的缔合基序。计算的缔合速率常数在两个系统中是相当的，尽管实验亲和常数相差三个数量级（D。Tello等人，生物化学部21：943-946，1993; K. A. Hibbits等人，生物化学。33：35843590，1994）。模拟表明，在亲和力的差异的起源来自解离速率常数。我们还对许多突变抗体片段-MEL结合进行了模拟实验，以解决静电的作用，并在有限程度上解决结合的方向方面。
Association rate constants for antigen/antibody associations have been computed by Brownian Dynamics simulations of D. L. Ermak and J. A. McCammon, J. Chem. Phys. 69:1352-1360, 1978. The model of monoclonal antibody (mAb) D44.1 is based on crystallographic data (B. C. Braden et at., J. Mol. Biol 243:767-781, 1994). Electrostatic forces that steer the antigen to the antibody-combining site are computed by solving the linearized Poisson-Boltzmann equation. D44.1-HEL complex displays very similar association motifs to a related anti-lysozyme antibody, HyHEL-5-HEL system. The computed association rate constants are comparable in the two systems, although the experimental affinity constants differ by three orders of magnitude (D. Tello et al., Biochem. Sec. Trans. 21:943-946, 1993; K. A. Hibbits et al., Biochemistry. 33:35843590, 1994). Simulations suggest that the origin of the differences in the affinity come from dissociation rate constants. We have also carried out simulation experiments on a number of mutant antibody fragment-MEL associations to address the role of electrostatics and, to a limited extent, the orientational aspects of association.