Naslov
New zinc ion parameters suitable for classical MD simulations of zinc metallo-peptidases

Autori
Tomić, Antonija ; Horvat, Gordan ; Ramek, Michael ; Agić, Dejan ; Brkić, Hrvoje ; Tomić, Sanja

Izvornik
Journal of chemical information and modeling (1549-9596) 59 (2019), 8; 3437-3453

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
metallo-peptidase ; human dipeptidyl peptidase III ; thermolysin ; neprilysin ; aminopeptidase N ; molecular dynamic simulations ; quantum mechanics – molecular mechanics ; nonbonded model ; hybrid bonded/nonbonded model ; cationic dummy atom model ; polarizable potential ; zinc ion parameters ; zinc ion coordination ; second metal ion coordination sphere

Sažetak
The main aim of this work was to find parameters for the zinc ion in human dipeptidyl peptidase III (DPP III) active site that would enable its reliable modeling. Since the parameters publicly available failed to reproduce the zinc ion coordination in the enzyme, we developed a new set of the hybrid bonded/nonbonded parameters for the zinc ion suitable for molecular modeling of the human DPP III, dynamics and ligand binding. The parameters allowed exchange of the water molecules coordinating the zinc ion and showed to be robust enough to enable reliable modeling not only human DPP III and its orthologues but also of the other zinc dependent peptidases with the zinc ion coordination similar to that in dipeptidyl peptidases III, i. e peptidases with the zinc ion coordinated with two histidines and one glutamate. The new parameters were tested on a set of 21 different systems comprising eight different peptidases, five DPP III orthologues, thermolysin, neprilysin and aminopeptidase N, and the results are summarized in the second part of the publication.

Izvorni jezik
Engleski

Znanstvena područja
Fizika, Kemija

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