Journal Article

FZJ-2021-04185

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Photopharmacology of Ion Channels through the Light of the Computational Microscope

Nin-Hill, A. ; Mueller, N. P. F.FZJ* ; Molteni, C. ; Rovira, C. ; Alfonso-Prieto, M. (Corresponding author)FZJ*

2021
Molecular Diversity Preservation International Basel

This record in other databases:      

Please use a persistent id in citations: http://hdl.handle.net/2128/29210  doi:10.3390/ijms222112072

Abstract: The optical control and investigation of neuronal activity can be achieved and carried out with photoswitchable ligands. Such compounds are designed in a modular fashion, combining a known ligand of the target protein and a photochromic group, as well as an additional electrophilic group for tethered ligands. Such a design strategy can be optimized by including structural data. In addition to experimental structures, computational methods (such as homology modeling, molecular docking, molecular dynamics and enhanced sampling techniques) can provide structural insights to guide photoswitch design and to understand the observed light-regulated effects. This review discusses the application of such structure-based computational methods to photoswitchable ligands targeting voltage- and ligand-gated ion channels. Structural mapping may help identify residues near the ligand binding pocket amenable for mutagenesis and covalent attachment. Modeling of the target protein in a complex with the photoswitchable ligand can shed light on the different activities of the two photoswitch isomers and the effect of site-directed mutations on photoswitch binding, as well as ion channel subtype selectivity. The examples presented here show how the integration of computational modeling with experimental data can greatly facilitate photoswitchable ligand design and optimization. Recent advances in structural biology, both experimental and computational, are expected to further strengthen this rational photopharmacology approach.

---

Contributing Institute(s):

1. Computational Biomedicine (IAS-5)
2. Computational Biomedicine (INM-9)

Research Program(s):

1. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)
2. 5251 - Multilevel Brain Organization and Variability (POF4-525) (POF4-525)
3. 5252 - Brain Dysfunction and Plasticity (POF4-525) (POF4-525)
4. DFG project 291198853 - FOR 2518: Funktionale Dynamik von Ionenkanälen und Transportern - DynIon - (291198853)

Appears in the scientific report 2021

---

Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF < 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---