Pore-level Quantitative Structure-Activity Relationship (QSAR) for Water Permeation Rate in Aquaporins

TL;DR

This paper introduces a pore-level QSAR model that links structural pore features with water permeation rates in aquaporins, aiding the design of biomimetic filtration membranes and enhancing understanding of their biological function.

Contribution

It presents a novel multi-feature QSAR framework that identifies key pore descriptors influencing water transport, expanding beyond single-feature analyses.

Findings

Recapitulates known determinants of water permeation in AQPs

Highlights new pore descriptors relevant in a multi-variable context

Provides a proof of concept for pore-level QSAR modeling

Abstract

Aquaporins (AQPs) and aquaglyceroporins (AQGPs) play a crucial role in regulating water transport and solute selectivity across biological membranes. Besides their biological relevance, AQPs have at-tracted growing interest as models for the design of next-generation biomimetic membranes for water filtration. In this work, we present a pore-level Quantitative Structure-Activity Relationship (QSAR) approach that relates structural and physicochemical pore descriptors with experimentally reported water permeation rates across a set of AQ(G)Ps with high-resolution 3D structures. This data-driven methodology, presented here as a proof of concept, introduces a multi-feature framework for determining pore descriptors associated with water transport efficiency in AQ(G)Ps. Applied to two compiled permeation rate datasets, this framework recapitulates determinants previously reported in single-feature studies, while also highlighting additional pore descriptors that emerge as relevant in a multi-variable context. The insights gained through this approach may, in perspective, contribute to advancing the rational design of AQP-based filtration devices and to deepening the molecular understanding of the function of these valuable macromolecules in health and disease.