free-binding energies and molecular interac3ons of
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Free-bindingenergiesandmolecularinterac3onsofyessotoxininthevoltage-gatedsodiumchannelNaV1.5:aninsilicoapproach
Several marine dinoflagellates produce unique secondary metabolites with intriguing biological ac3vi3es.Yessotoxin (YTX) and analogs are produced by three species ofmarine dinoflagellates, with potent ion-channelac3vity.ThisstudyaimedtoevaluatetheaffinityofYTXfortheNaV1.5channel,usinginsilicomodellingtools.
INTRODUCTION
Significant interac3ons and low binding free energies (ΔG), between-6.79and-10.32Kcalmol-1forYTXintheNaV1.5proteinmodel.Certainaminoacid residues inDomains I and IIwere reached, indica3ng thatthistoxinisapoten3alNaV1.5modulator.
MATERIALSANDMETHODS
AlignmentSelec3onCoverage
UniProtQ14524
HomosapiensSequencesearch
Swissmodelh]ps://
swissmodel.expasy.org/
Homologymodeling
Basicandtheoricalstructure
Primarychannelstructure
Func3onalvalida3on
Modelrefinement
Structuralvalida3on
Characteriza3on&valida3on
MolecularDocking
Blinddocking
126x126x126ÅBindingfree
energy
AutoDockToolsTriplicates
Dataanalysis
AutoDockTools1.5.6
Conforma3ons Interac3ons
Region1Region2
Region3Region4
Region5
This study cons3tutes the first approach to in silico explora3on ofpolyke3de-derived dinoflagellate toxins in pursuit of evalua3ng theirtherapeu3cpoten3al.
-15
-10
-5
0Region1 Region2 Region3 Region4 Region5
Bind
ingfreeene
rgy
(ΔGKcal·m
ol-1)
Simula5onregions
010203040
Region1 Region2 Region3 Region4 Region5
%cluster
Interaction of YTX in DI and DII of NaV1.5. YTX (pink) and different amino acids (blue)
AverageΔG=-10.3Kcalmol-1
RESULTS
What’snext?Tounderstand theeffectsofYTXon thevoltage-gatedsodium channel different studies are needed, i.e. electrophysiologyandmoleculardynamicsanalyses
Thanksto:
MaríadelCarmenOsorio-Ramírez1,LorenaMaríaDurán-Riveroll2,3,AllanD.Cembella3,andJoséCorrea-Basurto11LaboratoriodeDiseñoyDesarrollodeNuevosFármacoseInnovaciónBiotecnológica,SeccióndeEstudiosdePosgradoeInves3gación.EscuelaSuperiordeMedicina,Ins3tutoPolitécnicoNacional,CiudaddeMéxico,México;2CONACyT-DepartamentodeBiotecnologíaMarina,CentrodeInves3gaciónCientficaydeEducaciónSuperiordeEnsenada,BajaCalifornia,México;3Alfred-Wegener-Ins3tut,Helmholtz-ZentrumfürPolar-undMeeresforschung,Bremerhaven,Germany
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