期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 308, 期 -, 页码 216-223出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2019.05.047
关键词
AChE; Drug discovery; Affinity evaluation; Scoring function; Inhibition constant
资金
- Croatian Science Foundation [HrZZ-IP-2013-11-4307]
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 (K-i or IC50) in a broad range 10(-3) - 10(-12) M. The linear correlation model resulted in the highest coefficient of determination (r(2)) for the PLP2 function, 0.591. The LigScore1 function resulted in the lowest r(2) 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 sp(2) hybridized atoms in the ligand. A high coefficient of determination (r(2) > 0.5) was calculated for the following parameters: the number of heavy atoms, molecular mass, and number of atoms with sp(2) 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.
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