MI 3: Zavrimo COVID-19 – Iskanje molekul, ki se vežejo na RBD domeno glikoproteina S virusa SARS-CoV-2

Seznam tarč:

#26 2ajf – Structure of SARS coronavirus spike receptor-binding domain complexed with its receptor.

#27 2dd8 – Crystal Structure of SARS-CoV Spike Receptor-Binding Domain Complexed with Neutralizing Antibody

#28 3scl – Crystal structure of spike protein receptor-binding domain from SARS coronavirus epidemic strain complexed with human-civet chimeric receptor ACE2

#29 5×58 – Prefusion structure of SARS-CoV spike glycoprotein, conformation 1

#30 6ack –Trypsin-cleaved and low pH-treated SARS-CoV spike glycoprotein and ACE2 complex, ACE2-bound conformation 3

#31 6lzg – Structure of novel coronavirus spike receptor-binding domain complexed with its receptor ACE2

#32 6m17 – The 2019-nCoV RBD/ACE2-B0AT1 complex

#33 6m0j – Crystal structure of SARS-CoV-2 spike receptor-binding domain bound with ACE2

#34 6vw1 – Structure of SARS-CoV-2 chimeric receptor-binding domain complexed with its receptor human ACE2

OPIS MISIJE: Izbrali smo devet struktur RBD domene proteina glikoproteina S virusa SARS-CoV/SARS-CoV-2 v kompleksih z ACE2 receptorjem (6vw1, 6m0j, 6m17, 6ack, 3scl, 2ajf)  ali protitelesom (2dd8). Za pripravo izhodiščnih struktur smo najprej uporabili programYASARA/Structure. RBD domene posameznih proteinskih kompleksov smo prekrili, ter preverili kateri AK ostanki sodelujejo pri interakciji z ACE2, na osnovi teh imformacij smo sedaj omejili območje kamor smo sidrali ligande iz knjižnice 10M+ spojin.

Za sidranje smo uporabili program RxDOCK, ki smo ga poganjali preko sistema za distribucijsko računanje.

Zanimiv rezultat smo dobili s sidranjem konformacijsko omejenih  peptidov v vezavno mesto domene RBD proteina. Glej sliko 1:

Slika 1: Vezava konformacijsko omejenega dodekapeptida na RBD domeno glikoproteina Spike virusa SARS-CoV-2.