Naslov
Monte Carlo docking of quinuclidine derivatives against cholinesterases

Autori
Mikelić, Ana ; Primožič, Ines ; Hrenar, Tomica

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
7th Faculty of Science PhD Students Symposium Book of Abstracts / Pavlek, Katarina - Zagreb : Prirodoslovno-matematički fakultet Sveučilišta u Zagrebu, 2023, 116-116

ISBN
978-953-6067-01-7

Skup
7th Faculty of Science PhD Students Symposium

Mjesto i datum
Zagreb, Hrvatska, 21.04.2023. - 22.04.2023

Vrsta sudjelovanja
Poster

Vrsta recenzije
Recenziran

Ključne riječi
monte carlo docking ; stochastic search ; cholinesterase inhibitors ; quinuclidine carbamates

Sažetak
In a recent study, quinuclidine-based carbamates showed significant anti-acetylcholinesterase and anti-butyrylcholinesterase activity, making them promising central nervous system agents [1]. Binding modes of selected quinuclidine derivatives within cholinesterase’s active site were investigated by Monte Carlo quantum chemical docking. The configurational space of each ligand was spanned in 3 translational, 3 rotational, as well as all relevant torsional degrees of freedom and sampled using an implemented stochastic search algorithm [2]. The protein was kept rigid during the docking process while small molecules were allowed to explore the active site. For every generated configuration, single-point calculations were performed using the semiempirical PM7 Hamiltonian. Lowest-energy Michaelis complexes were singled out and optimized at a higher level of theory. Combined QM/QM optimizations were conducted using the ONIOM method and relative standard Gibbs energies of binding were calculated. All quantum chemical calculations were performed using the Gaussian 16 program package [3].

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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