Wold S, Hellberg S, Dunn W J
Acta Pharmacol Toxicol (Copenh). 1983;52 Suppl 2:158-89. doi: 10.1111/j.1600-0773.1983.tb02689.x.
The prediction of the biological activity of chemical compounds by means of mathematical models is discussed. Biological activity of chemicals, including their toxicity on man and other biological organisms and systems, involves too complex phenomena to presently be predictable by fundamental models such as ab initio quantum mechanical models or statistical mechanical models. Hence one takes recourse to semi-empirical and empirical models which relate the variation in chemical structure of chemical compounds to the variation in their measured biological activity, e.g. toxicity in one or several test systems. These models are "calibrated" on series of similar compounds with "known" toxicity, the training set. Thereafter the models can--in fortunate cases--be used to predict the toxicity of compounds which are structurally similar to the training set compounds. The formulation and applicability of semi-empirical and empirical models relating chemical structure to biological activity is discussed. Causes and remedies for commonly encountered fallacies are presented.
讨论了利用数学模型预测化合物生物活性的问题。化学物质的生物活性，包括其对人类和其他生物有机体及系统的毒性，涉及过于复杂的现象，目前无法通过诸如从头算量子力学模型或统计力学模型等基础模型进行预测。因此，人们求助于半经验模型和经验模型，这些模型将化合物化学结构的变化与它们所测得的生物活性变化联系起来，例如在一个或几个测试系统中的毒性。这些模型在具有“已知”毒性的一系列相似化合物（训练集）上进行“校准”。此后，在幸运的情况下，这些模型可用于预测结构与训练集化合物相似的化合物的毒性。讨论了将化学结构与生物活性相关的半经验模型和经验模型的构建及适用性。介绍了常见错误的原因及补救方法。
