Vásquez Andrés Felipe, González Barrios Andrés
Grupo de Diseño de Productos y Procesos (GDPP), School of Chemical Engineering, Universidad de los Andes, Bogotá, Colombia.
Laboratorio de Fisiología Molecular, Instituto Nacional de Salud, Bogotá, Colombia.
Front Chem. 2019 Aug 16;7:564. doi: 10.3389/fchem.2019.00564. eCollection 2019.
The ligand efficiency (LE) indexes have long been used as decision-making criteria in drug discovery and development. However, in the context of fragment-based drug design (FBDD), these metrics often exhibit a strong emphasis toward the selection of highly efficient "core" fragments for potential optimization, which are not usually considered as parts of a larger molecule with a size typical for a drug. In this study, we present a relative group contribution (RGC) model intended to predict the efficiency of a drug-sized compound in terms of its component fragments. This model could be useful not only in rapidly predicting all the possible combinations of promising fragments from an earlier hit discovery stage, but also in enabling a relatively low-LE fragment to become part of a drug-sized compound as long as it is "rescued" by other high-LE fragments.
配体效率（LE）指标长期以来一直被用作药物发现和开发中的决策标准。然而，在基于片段的药物设计（FBDD）背景下，这些指标通常强烈倾向于选择高效的“核心”片段以进行潜在优化，而这些片段通常不被视为具有典型药物大小的更大分子的一部分。在本研究中，我们提出了一种相对基团贡献（RGC）模型，旨在根据其组成片段预测药物大小化合物的效率。该模型不仅可用于在早期命中发现阶段快速预测有前景片段的所有可能组合，而且还能使低LE片段只要被其他高LE片段“拯救”，就能够成为药物大小化合物的一部分。
