QSAR Development for Plasma Protein Binding: Influence of the Ionization State.

ABSTRACT:

Purpose

This study explored several strategies to improve the performance of literature QSAR models for plasma protein binding (PPB), such as a suitable endpoint transformation, a correct representation of chemicals, more consistency in the dataset, and a reliable definition of the applicability domain.

Methods

We retrieved human fraction unbound (Fu) data for 670 compounds from the literature and carefully checked them for consistency. Descriptors were calculated taking account of the ionization state of molecules at physiological pH (7.4), in order to better estimate the affinity of molecules to blood proteins. We used different algorithms and chemical descriptors to explore the most suitable strategy for modeling the endpoint. SMILES (simplified molecular input line entry

SUBMITTER: Toma C 

PROVIDER: S-EPMC6308215 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature