Influence of Descriptor Implementation on Compound Ranking Based on Multiparameter Assessment,Journal of Chemical Information and Modeling

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Influence of Descriptor Implementation on Compound Ranking Based on Multiparameter Assessment
Journal of Chemical Information and Modeling ( IF 5.6 ) Pub Date : 2018-04-24 00:00:00 , DOI: 10.1021/acs.jcim.7b00734
Ekaterina A. Sosnina _{1,

2,

3} , Dmitry I. Osolodkin _{1,

4,

5} , Eugene V. Radchenko _{1,

3} , Sergey Sosnin _{2,

3} , Vladimir A. Palyulin _{1,

3}

Affiliation

Most of the common molecular descriptors have numerous different implementations. This can influence the results of compound prioritization based on the multiparameter assessment (MPA) approach that allows a medicinal chemist to simultaneously analyze and achieve the desired balance of the diverse and often conflicting molecular and pharmacological properties. In this study, we analyzed the feasibility of using different implementations of common descriptors (logP, logS, TPSA, logBB, hERG, nHBA) interchangeably in predesigned sets of requirements in the course of multiparameter compound optimization. The influence of methods of descriptor calculation, continuity or discreteness of their values, their applicability domains, as well as of the nature of desirability functions in an MPA profile were examined in terms of the stability of MPA compound ranking. It was shown that the interchangeable use of different methods of descriptor calculation is reliably acceptable only for continuously distributed parameters transformed by a smooth desirability function. If a descriptor in an MPA scheme is discretely distributed, only the implementation that was used for building the scoring profile may be used for assessment. An inconsistency of assessment due to different applicability domains of descriptors was also demonstrated.

中文翻译：

基于多参数评估的描述符实现对复合词排名的影响

大多数常见的分子描述符具有许多不同的实现。这可能会影响基于多参数评估（MPA）方法的化合物优先排序的结果，该方法使药用化学家可以同时分析并实现所需的多种多样且经常相互冲突的分子和药理特性之间的平衡。在这项研究中，我们分析了在多参数化合物优化过程中，在预先设计的一组需求中互换使用公共描述符（logP，logS，TPSA，logBB，hERG，nHBA）的不同实现的可行性。描述符计算方法的影响，其值的连续性或离散性，其适用范围，根据MPA化合物排名的稳定性，对MPA配置文件中的期望功能以及其功能的性质进行了检查。结果表明，仅对于通过平滑期望函数转换的连续分布参数，可以可靠地接受使用不同的描述符计算方法的互换使用。如果MPA方案中的描述符是离散分布的，则只有用于构建评分资料的实施方案才可以用于评估。还说明了由于描述符的适用范围不同而导致的评估不一致。如果MPA方案中的描述符是离散分布的，则只有用于构建评分资料的实施方案才可以用于评估。还说明了由于描述符的适用范围不同而导致的评估不一致。如果MPA方案中的描述符是离散分布的，则只有用于构建评分资料的实施方案才可以用于评估。还说明了由于描述符的适用范围不同而导致的评估不一致。

更新日期：2018-04-24

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