Ekhteiari Salmas, Ramin, et al. "Virtual Screening of Small Molecules Databases for Discovery of Novel PARP-1 Inhibitors: Combination of in Silico and in Vitro Studies." Journal of Biomolecular Structure & Dynamics, vol. 35, no. 9, 2017, pp. 1899-1915.
Ekhteiari Salmas R, Unlu A, Bektaş M, et al. Virtual screening of small molecules databases for discovery of novel PARP-1 inhibitors: combination of in silico and in vitro studies. J Biomol Struct Dyn. 2017;35(9):1899-1915.
Ekhteiari Salmas, R., Unlu, A., Bektaş, M., Yurtsever, M., Mestanoglu, M., & Durdagi, S. (2017). Virtual screening of small molecules databases for discovery of novel PARP-1 inhibitors: combination of in silico and in vitro studies. Journal of Biomolecular Structure & Dynamics, 35(9), 1899-1915. https://doi.org/10.1080/07391102.2016.1199328
Ekhteiari Salmas R, et al. Virtual Screening of Small Molecules Databases for Discovery of Novel PARP-1 Inhibitors: Combination of in Silico and in Vitro Studies. J Biomol Struct Dyn. 2017;35(9):1899-1915. PubMed PMID: 27315035.
TY - JOUR
T1 - Virtual screening of small molecules databases for discovery of novel PARP-1 inhibitors: combination of in silico and in vitro studies.
AU - Ekhteiari Salmas,Ramin,
AU - Unlu,Ayhan,
AU - Bektaş,Muhammet,
AU - Yurtsever,Mine,
AU - Mestanoglu,Mert,
AU - Durdagi,Serdar,
Y1 - 2016/07/17/
PY - 2016/6/18/pubmed
PY - 2018/3/16/medline
PY - 2016/6/18/entrez
KW - E-pharmacophore
KW - MM-PBSA
KW - PARP-1
KW - QM-polarized ligand docking
KW - free energy perturbation calculations
KW - high-throughput virtual screening
KW - in vitro colorimetric assay
KW - molecular docking simulations
KW - molecular dynamics (MD) simulations
SP - 1899
EP - 1915
JF - Journal of biomolecular structure & dynamics
JO - J Biomol Struct Dyn
VL - 35
IS - 9
N2 - Poly(ADP-ribose) polymerase-1 (PARP-1) enzyme has critical roles in DNA replication repair and recombination. Thus, PARP-1 inhibitors play an important role in the cancer therapy. In the current study, we have performed combination of in silico and in vitro studies in order to discover novel inhibitors against PARP-1 target. Structure-based virtual screening was carried out for an available small molecules database. A total of 257,951 ligands from Otava database were screened at the binding pocket of PARP-1 using high-throughput virtual screening techniques. Filtered structures based on predicted binding energy results were then used in more sophisticated molecular docking simulations (i.e. Glide/standard precision, Glide/XP, induced fit docking - IFD, and quantum mechanics polarized ligand docking - QPLD). Potential high binding affinity compounds that are predicted by molecular simulations were then tested by in vitro methods. Computationally proposed compounds as PARP-1 inhibitors (Otava Compound Codes: 7111620047 and 7119980926) were confirmed by in vitro studies. In vitro results showed that compounds 7111620047 and 7119980926 have IC50 values of 0.56 and 63 μM against PARP-1 target, respectively. The molecular mechanism analysis, free energy perturbation calculations using long multiple molecular dynamics simulations for the discovered compounds which showed high binding affinity against PARP-1 enzyme, as well as structure-based pharmacophore development (E-pharmacophore) studies were also studied.
SN - 1538-0254
UR - https://www.unboundmedicine.com/medline/citation/27315035/Virtual_screening_of_small_molecules_databases_for_discovery_of_novel_PARP_1_inhibitors:_combination_of_in_silico_and_in_vitro_studies_
DB - PRIME
DP - Unbound Medicine