Naslov
Novel radial distribution function approach in the study of point mutations: the HIV-1 protease case study

Autori
Novak, Jurica ; Grishina, Maria A. ; Potemkin, Vladimir A.

Izvornik
Future Medicinal Chemistry (1756-8919) 12 (2020), 11; 1025-1036

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

Ključne riječi
drug design ; HIV-1 protease ; inhibitors ; mutations ; QSAR ; radial distribution function ; RDF

Sažetak
Background: Mutations are one of the engines of evolution. Under constant stress pressure, mutations can lead to the emergence of unwanted, drug resistant entities. Methodology: The radial distribution func- tion weighted by the number of valence shell electrons is used to design quantitative structure–activity relationship (QSAR) model relating descriptors with the inhibition constant for a series of wild-type HIV- 1 protease inhibitor complexes. The residuals of complexes with mutant HIV-1 protease were correlated with the energy of the highest occupied molecular orbitals of the residues introduced to enzyme via point mutations. Conclusion: Successful identification of residues Ile3, Asp25, Val32 and Ile50 as the one whose substitution influences the inhibition constant the most, demonstrates the potential of the pro- posed methodology for the study of the effects of point mutations.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Interdisciplinarne prirodne znanosti, Farmacija

POVEZANOST RADA