Richard A M, Rabinowitz J R, Waters M D
Genetic Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Mutat Res. 1989 Nov;221(3):181-96. doi: 10.1016/0165-1110(89)90035-3.
The relationship between computational SAR studies and relevant data gathering and generation activities is complex. First, the chemical class to be studied is selected on the basis of information requirements for hazard identification and assessment. Membership in the class is determined by consideration of chemical structure and reactivity. Compilation of the existing bioassay data for this chemical class follows immediately from the specification of the class. Bioassay data, qualitative knowledge of general chemical reactivities in this class, and knowledge concerning potential interactions with biomolecular targets all contribute to the derivation of possible mechanisms for biological activity. Computational studies based on modeling the proposed mechanism of action and/or the existing data base can provide a quantitative basis for the differentiation between chemicals. There is the opportunity for continuing feedback between the quantitative computational studies and the development of a relevant bioassay data base for this chemical class. The qualitative and quantitative information on the potential biological responses obtained will provide a rational basis for extrapolation from the extant data base to the chemicals of interest, and to biological responses significant to the assessment for which complete data are unavailable. Knowledge concerning possible mechanisms of action and preexisting data determine the type of computational study that will be most useful.
计算比吸收率（SAR）研究与相关数据收集和生成活动之间的关系很复杂。首先，要根据危害识别和评估的信息需求来选择待研究的化学类别。该类别的成员资格是通过考虑化学结构和反应性来确定的。在确定该化学类别后，紧接着就要汇编该类别现有的生物测定数据。生物测定数据、对该类别中一般化学反应性的定性知识以及有关与生物分子靶点潜在相互作用的知识，都有助于推导可能的生物活性机制。基于对所提出的作用机制和/或现有数据库进行建模的计算研究，可以为区分化学物质提供定量依据。在定量计算研究与为该化学类别开发相关生物测定数据库之间，存在持续反馈的机会。所获得的关于潜在生物反应的定性和定量信息，将为从现有数据库外推至感兴趣的化学物质以及对那些缺乏完整数据的评估而言具有重要意义的生物反应，提供合理依据。关于可能的作用机制的知识和先前存在的数据，决定了最有用的计算研究类型。
