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@ARTICLE{AlfonsoPrieto:1008229,
author = {Alfonso-Prieto, Mercedes and Capelli, Riccardo},
title = {{M}achine {L}earning-{B}ased {M}odeling of {O}lfactory
{R}eceptors in {T}heir {I}nactive {S}tate: {H}uman
{OR}51{E}2 as a {C}ase {S}tudy},
journal = {Journal of chemical information and modeling},
volume = {63},
number = {10},
issn = {0095-2338},
address = {Washington, DC},
publisher = {American Chemical Society},
reportid = {FZJ-2023-02263},
pages = {2911 - 2917},
year = {2023},
note = {Open access publication; open access fee paid by Italy. FZJ
author supported in part by the DFG Research Unit FOR2518
“Functional Dynamics of Ion Channels and Transporters –
DynIon” (291198853), Project P6 (329460521).},
abstract = {Atomistic-level investigation of olfactory receptors (ORs)
is a challenging task due to the experimental/computational
difficulties in the structural determination/prediction for
members of this family of G-protein coupled receptors. Here,
we have developed a protocol that performs a series of
molecular dynamics simulations from a set of structures
predicted de novo by recent machine learning algorithms and
apply it to a well-studied receptor, the human OR51E2. Our
study demonstrates the need for simulations to refine and
validate such models. Furthermore, we demonstrate the need
for the sodium ion at a binding site near D2.50 and E3.39 to
stabilize the inactive state of the receptor. Considering
the conservation of these two acidic residues across human
ORs, we surmise this requirement also applies to the other
400 members of this family. Given the almost concurrent
publication of a CryoEM structure of the same receptor in
the active state, we propose this protocol as an in silico
complement to the growing field of ORs structure
determination.},
cin = {INM-9 / IAS-5},
ddc = {540},
cid = {I:(DE-Juel1)INM-9-20140121 / I:(DE-Juel1)IAS-5-20120330},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524) / DFG project 291198853 - FOR 2518: Funktionale
Dynamik von Ionenkanälen und Transportern - DynIon -
(291198853) / DFG project 329460521 - Protonentransfer und
Substraterkennung in SLC17-Transportern (329460521)},
pid = {G:(DE-HGF)POF4-5241 / G:(GEPRIS)291198853 /
G:(GEPRIS)329460521},
typ = {PUB:(DE-HGF)16},
pubmed = {37145455},
UT = {WOS:000985641000001},
doi = {10.1021/acs.jcim.3c00380},
url = {https://juser.fz-juelich.de/record/1008229},
}