Leveraging Quantum Mechanical Properties to Predict Solvent Effects on Large Drug-Like Molecules

Publikation: Beitrag in Buch/Konferenzbericht/Sammelband/GutachtenBeitrag in KonferenzbandBeigetragenBegutachtung

Beitragende

Abstract

Understanding how solvation affects structure-property and property-property relationships of drug-like molecules is crucial for de novo design, as most relevant reactions occur in aqueous environments. We have thus performed an exhaustive analysis of the recently proposed Aquamarine dataset to gain insights into the effect of solvent-molecule interaction on the quantum-mechanical (QM) properties of large drug-like molecules. Our results show that the inclusion of an implicit solvent model of water changes the values of (extensive and intensive) QM properties but it does not alter the correlations among them. Moreover, we have found that solvation can limit the identification of unique molecular conformations, with variations in specific properties being rationalized by the extent of structural changes. Δ-learning approach was used to predict solvent effects on the dipole moment μ and the many-body dispersion energy EMBD, resulting in more accurate and scalable predictive models compared to these directly trained on solvated properties. Hence, our work provides valuable insights into the effect of solvent-molecule interaction on physicochemical properties, which could assist in the development of machine-learning models for designing solvated molecules of pharmaceutical and biological relevance.

Details

OriginalspracheEnglisch
TitelAI in Drug Discovery
Redakteure/-innenDjork-Arné Clevert, Michael Wand, Jürgen Schmidhuber, Kristína Malinovská, Igor V. Tetko
Herausgeber (Verlag)Springer Science and Business Media B.V.
Seiten47-57
Seitenumfang11
ISBN (elektronisch)978-3-031-72381-0
ISBN (Print)978-3-031-72380-3
PublikationsstatusVeröffentlicht - 2025
Peer-Review-StatusJa

Publikationsreihe

ReiheLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Band14894 LNCS
ISSN0302-9743

Workshop

Titel1st International Workshop on AI in Drug Discovery
KurztitelAIDD 2024
Veranstaltungsnummer1
Beschreibungheld as a part of the 33rd International Conference on Artificial Neural Networks, ICANN 2024
Dauer19 September 2024
Webseite
OrtUSI-SUPSI Campus Est
StadtLugano-Viganello
LandSchweiz

Externe IDs

ORCID /0000-0002-7673-3142/work/181861247

Schlagworte

Schlagwörter

  • Drug-like molecules, Property prediction, Quantum-mechanical properties, Solvent effects