Naslov
Assessment of scoring functions and in silico parameters for AChE-ligand interactions as a tool for predicting inhibition potency

Autori
Šinko, Goran

Izvornik
Chemico-biological interactions (0009-2797) 308 (2019); 216-223

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

Ključne riječi
AChE ; drug discovery ; affinity evaluation, scoring function ; inhibition constant

Sažetak
In this study, 68 crystal structures of complexes between acetylcholinesterase (AChE, EC 3.1.1.7) and its ligands, deposited in the PDB, were analyzed by scoring the functions: LigScore1, LigScore2, PLP1, PLP2, Jain, PMF and PMF04. The scores derived from scoring functions were correlated with an inhibition constant for each ligand (Ki or IC50) in a broad range 10-3 – 10-12 M. The linear correlation model resulted in the highest coefficient of determination (r2) for the PLP2 function, 0.591. The LigScore1 function resulted in the lowest r2 value of 0.226. The PubChem database was the source of in silico computed ligand properties which were then correlated with an inhibition constant for each ligand. For the purposes of this study, two additional non-PubChem parameters were evaluated: total and relative number of sp2 hybridized atoms in the ligand. A high coefficient of determination (r2>0.5) was calculated for the following parameters: the number of heavy atoms, molecular mass, and number of atoms with sp2 hybridization. The PLP2 scoring function is a good candidate for drug discovery related to AChE, although a better scoring function could be developed with a higher number of crystal structures of AChE complexes and more reliable kinetic data.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA