Predicting antimicrobial activity of conjugated oligoelectrolyte molecules via machine learning

TL;DR

This paper presents a machine learning model to predict the antimicrobial activity of conjugated oligoelectrolyte molecules, a novel antibiotic class, achieving good accuracy without prior mechanistic knowledge, and highlights the importance of molecular representation.

Contribution

The study introduces a predictive model for conjugated oligoelectrolytes' antimicrobial activity using optimized molecular descriptors, applicable to novel antibiotic classes.

Findings

Achieved an R2 of 0.65 in predicting activity against E. coli.

Identified 3D molecular shape as critical for accurate predictions.

Demonstrated model adaptability to other novel antibiotics.

Abstract

New antibiotics are needed to battle growing antibiotic resistance, but the development process from hit, to lead, and ultimately to a useful drug, takes decades. Although progress in molecular property prediction using machine-learning methods has opened up new pathways for aiding the antibiotics development process, many existing solutions rely on large datasets and finding structural similarities to existing antibiotics. Challenges remain in modelling of unconventional antibiotics classes that are drawing increasing research attention. In response, we developed an antimicrobial activity prediction model for conjugated oligoelectrolyte molecules, a new class of antibiotics that lacks extensive prior structure-activity relationship studies. Our approach enables us to predict minimum inhibitory concentration for E. coli K12, with 21 molecular descriptors selected by recursive elimination from a set of 5,305 descriptors. This predictive model achieves an R2 of 0.65 with no prior knowledge of the underlying mechanism. We find the molecular representation optimum for the domain is the key to good predictions of antimicrobial activity. In the case of conjugated oligoelectrolytes, a representation reflecting the 3-dimensional shape of the molecules is most critical. Although it is demonstrated with a specific example of conjugated oligoelectrolytes, our proposed approach for creating the predictive model can be readily adapted to other novel antibiotic candidate domains.