The molecular modeling of novel inhibitors of protein tyrosine phosphatase 1B based on catechol by MD and MM-GB (PB)/SA calculations
Yükleniyor...
Tarih
2014
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Korean Chemical Society
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Binding modes of a series of catechol derivatives such as protein tyrosine phosphatase 1B (PTP1B) inhibitors
were identified by molecular modeling techniques. Docking, molecular dynamics simulations and free energy
calculations were employed to determine the modes of these new inhibitors. Binding free energies were
calculated by involving different energy components using the Molecular Mechanics-Poisson-Boltzmann
Surface Area and Generalized Born Surface Area methods. Relatively larger binding energies were obtained
for the catechol derivatives compared to one of the PTP1B inhibitors already in use. The Molecular Mechanics/
Generalized Born Surface Area (MM/GBSA) free energy decomposition analysis indicated that the hydroxyl
functional groups and biphenyl ring system had favorable interactions with Met258, Tyr46, Gln262 and
Phe182 residues of PTP1B. The results of hydrogen bound analysis indicated that catechol derivatives, in
addition to hydrogen bonding interactions, Val49, Ile219, Gln266, Asp181 and amino acid residues of PTP1B
are responsible for governing the inhibitor potency of the compounds. The information generated from the
present study should be useful for the design of more potent PTP1B inhibitors as anti-diabetic agents.
Açıklama
Anahtar Kelimeler
Binding free energy, Catechol, MM/GBSA, MM/PBSA, PTP1B inhibitors
Kaynak
Bulletin of the Korean Chemical Society
WoS Q Değeri
Q4
Scopus Q Değeri
Q2
Cilt
35
Sayı
6
Künye
Kocakaya, Ş. Ö. (2014). The molecular modeling of novel inhibitors of protein tyrosine phosphatase 1B based on catechol by MD and MM-GB (PB)/SA calculations. Bulletin of the Korean Chemical Society, 35(6), 1769-1776.
