PSW-Designer: An Open-Source Computational Platform for the Design and Virtual Screening of Photopharmacological Ligands

Icaro A Simon, Evert J Homan, Maikel Wijtmans, Michael Sundström, Rob Leurs, Iwan J P De Esch, Barbara A Zarzycka

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstract

Photoswitchable (PSW) molecules offer an attractive opportunity for the optical control of biological processes. However, the successful design of such compounds remains a challenging multioptimization endeavor, resulting in several biological target classes still relatively poorly explored by photoswitchable ligands, as is the case for G protein-coupled receptors (GPCRs). Here, we present the PSW-Designer, a fully open-source computational platform, implemented in the KNIME Analytics Platform, to design and virtually screen novel photoswitchable ligands for photopharmacological applications based on privileged scaffolds. We demonstrate the applicability of the PSW-Designer to GPCRs and assess its predictive capabilities via two retrospective case studies. Furthermore, by leveraging bioactivity information on known ligands, typical and atypical strategies for photoswitchable group incorporation, and the increasingly structural information available for biological targets, the PSW-Design will facilitate the design of novel photoswitchable molecules with improved photopharmacological properties and increased binding affinity shifts upon illumination for GPCRs and many other protein targets.

OriginalsprogEngelsk
TidsskriftJournal of Chemical Information and Modeling
Vol/bind63
Udgave nummer21
Sider (fra-til)6696-6705
Antal sider10
ISSN1549-9596
DOI
StatusUdgivet - 2023
Udgivet eksterntJa

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