Phillips D R, Moate P J, Boston R C
Biochemistry Department, La Trobe University, Bundoora, Vic., Australia.
Anticancer Drug Des. 1994 Jun;9(3):209-19.
A multicompartment simulation analysis (CONSAM) has been used to describe the in vitro inhibition of transcription of DNA by echinomycin. The model assumes that at all drug blockage sites the fractional amount of blocked RNA polymerase is defined by the relative drug occupancy at that site (and is released at a rate defined by the drug dissociation rate), with all remaining enzyme being rapidly transferred past that site. The solution to the 48 parameters (three per drug site, 16 sites), which fully described the echinomycin-DNA transcription data set, can readily be accomplished without manual intervention within an hour on a MS-DOS, 486D-based microcomputer, compared to several months for a similar solution by Monte-Carlo simulation (requiring repeated intervention). The adequacy of the parameters to describe the model was confirmed by four independent criteria. The approach is applicable to the analysis of any enzyme system where an inhibitor of any type (interacting in either a reversible or irreversible manner) prevents the processive movement of enzyme along the template.
一种多隔室模拟分析（CONSAM）已被用于描述棘霉素对DNA转录的体外抑制作用。该模型假定，在所有药物阻断位点，被阻断的RNA聚合酶的分数数量由该位点的相对药物占有率定义（并以药物解离速率定义的速率释放），而所有剩余的酶则迅速转移通过该位点。与通过蒙特卡罗模拟（需要反复干预）获得类似解决方案所需的数月时间相比，在基于MS-DOS 486D的微型计算机上，无需人工干预，一小时内即可轻松完成对48个参数（每个药物位点3个，共16个位点）的求解，这些参数充分描述了棘霉素-DNA转录数据集。通过四个独立标准证实了这些参数对模型描述的充分性。该方法适用于分析任何类型的抑制剂（以可逆或不可逆方式相互作用）阻止酶沿模板进行性移动的任何酶系统。
