Influence of Descriptor Implementation on Compound Ranking Based on Multiparameter Assessment

J Chem Inf Model. 2018 May 29;58(5):1083-1093. doi: 10.1021/acs.jcim.7b00734. Epub 2018 May 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Databases, Pharmaceutical*
  • Drug Discovery
  • Informatics / methods*
  • Quantitative Structure-Activity Relationship