Open AccessConstruction of a Full-Atomic Mechanistic Model of Human Apurinic/Apyrimidinic Endonuclease APE1 for Virtual Screening of Novel Inhibitors
Author(s) -
Ilyas G. Khaliullin,
D. K. Nilov,
И. В. Шаповалова,
V. K. Švedas
Publication year - 2012
Publication title -
acta naturae
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 26
ISSN - 2075-8251
DOI - 10.32607/actanaturae.10648
Subject(s) - ap site , dna (apurinic or apyrimidinic site) lyase , endonuclease , virtual screening , active site , molecular mechanics , chemistry , biochemistry , enzyme , dna repair , biophysics , dna , stereochemistry , biology , molecular dynamics , computational chemistry , drug discovery
A full-atomic molecular model of human apurinic/apyrimidinic endonuclease APE1, an important enzyme in the DNA repair system, has been constructed. The research consisted of hybrid quantum mechanics/ molecular mechanics modeling of the enzyme-substrate interactions, as well as calculations of the ionization states of the amino acid residues of the active site of the enzyme. The choice of the APE1 mechanism with an Asp210 residue as a proton acceptor was validated by means of a generalization of modeling and experimental data. Interactions were revealed in the active site that are of greatest significance for binding the substrate and potential APE1 inhibitors (potential co-drugs of interest in the chemo- and radiotherapy of oncological diseases).