TY  - JOUR
AU  - Nin-Hill, Alba
AU  - Mueller, Nicolas Pierre Friedrich
AU  - Molteni, Carla
AU  - Rovira, Carme
AU  - Alfonso-Prieto, Mercedes
TI  - Photopharmacology of Ion Channels through the Light of the Computational Microscope
JO  - International journal of molecular sciences
VL  - 22
IS  - 21
SN  - 1422-0067
CY  - Basel
PB  - Molecular Diversity Preservation International
M1  - FZJ-2021-04185
SP  - 12072 -
PY  - 2021
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:34769504
UR  - <Go to ISI:>//WOS:000720497000001
DO  - DOI:10.3390/ijms222112072
UR  - https://juser.fz-juelich.de/record/902331
ER  -