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Molecular docking studies of Traditional Chinese Medicinal compounds against known protein targets to treat non-small cell lung carcinomas.

Zhao GF, Huang ZA, Du XK, Yang ML, Huang DD, Zhang S - Mol Med Rep (2016)

Bottom Line: In silico drug design using virtual screening, absorption, distribution, metabolism and excretion (ADME)/Tox data analysis, automated docking and molecular dynamics simulations for the determination of lead compounds for further in vitro analysis is a cost effective strategy.The present study used this strategy to discover novel lead compounds from an in-house database of Traditional Chinese Medicinal (TCM) compounds against epithelial growth factor receptor (EGFR) protein for targeting non-small cell lung cancer (NSCLC).After virtual screening of an initial dataset of 2,242 TCM compounds, leads were identified based on binding energy and ADME/Tox data and subjected to automated docking followed by molecular dynamics simulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiothoracic Surgery, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China.

ABSTRACT
In silico drug design using virtual screening, absorption, distribution, metabolism and excretion (ADME)/Tox data analysis, automated docking and molecular dynamics simulations for the determination of lead compounds for further in vitro analysis is a cost effective strategy. The present study used this strategy to discover novel lead compounds from an in-house database of Traditional Chinese Medicinal (TCM) compounds against epithelial growth factor receptor (EGFR) protein for targeting non-small cell lung cancer (NSCLC). After virtual screening of an initial dataset of 2,242 TCM compounds, leads were identified based on binding energy and ADME/Tox data and subjected to automated docking followed by molecular dynamics simulation. Triptolide, a top compound identified by this vigorous in silico screening, was then tested in vitro on the H2347 cell line carrying wild-type EGFR, revealing an anti-proliferative potency similar to that of known drugs against NSCLC.

No MeSH data available.


Related in: MedlinePlus

Psi/phi distribution before and after EM. EM, energy minimization.
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f1-mmr-14-02-1132: Psi/phi distribution before and after EM. EM, energy minimization.

Mentions: The crystal structure of the kinase domain of the EGFR protein, ranging from amino acids 652–974, was observed using the SPDB viewer to identify missing amino acids and perform energy minimization. The Ramachandran plot before and after energy minimization shows the improved acceptability of the overall structure (Fig. 1), where points represent residues inside and outside the acceptable region, and the contours represent the hardsphere and overlap. The minimized structure of the domain was then processed using the VINA plugin of Pymol, where the grid around the ATP binding site was created. The grid box was subjected to screening of the Traditional Chinese Medicinal compound database (Ningbo No. 2 Hospital), which was useful for narrowing down the number of compounds based on their binding energy. The cutoff value of the ΔG used for initial screening was −9 kcal/mol.


Molecular docking studies of Traditional Chinese Medicinal compounds against known protein targets to treat non-small cell lung carcinomas.

Zhao GF, Huang ZA, Du XK, Yang ML, Huang DD, Zhang S - Mol Med Rep (2016)

Psi/phi distribution before and after EM. EM, energy minimization.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940108&req=5

f1-mmr-14-02-1132: Psi/phi distribution before and after EM. EM, energy minimization.
Mentions: The crystal structure of the kinase domain of the EGFR protein, ranging from amino acids 652–974, was observed using the SPDB viewer to identify missing amino acids and perform energy minimization. The Ramachandran plot before and after energy minimization shows the improved acceptability of the overall structure (Fig. 1), where points represent residues inside and outside the acceptable region, and the contours represent the hardsphere and overlap. The minimized structure of the domain was then processed using the VINA plugin of Pymol, where the grid around the ATP binding site was created. The grid box was subjected to screening of the Traditional Chinese Medicinal compound database (Ningbo No. 2 Hospital), which was useful for narrowing down the number of compounds based on their binding energy. The cutoff value of the ΔG used for initial screening was −9 kcal/mol.

Bottom Line: In silico drug design using virtual screening, absorption, distribution, metabolism and excretion (ADME)/Tox data analysis, automated docking and molecular dynamics simulations for the determination of lead compounds for further in vitro analysis is a cost effective strategy.The present study used this strategy to discover novel lead compounds from an in-house database of Traditional Chinese Medicinal (TCM) compounds against epithelial growth factor receptor (EGFR) protein for targeting non-small cell lung cancer (NSCLC).After virtual screening of an initial dataset of 2,242 TCM compounds, leads were identified based on binding energy and ADME/Tox data and subjected to automated docking followed by molecular dynamics simulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiothoracic Surgery, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China.

ABSTRACT
In silico drug design using virtual screening, absorption, distribution, metabolism and excretion (ADME)/Tox data analysis, automated docking and molecular dynamics simulations for the determination of lead compounds for further in vitro analysis is a cost effective strategy. The present study used this strategy to discover novel lead compounds from an in-house database of Traditional Chinese Medicinal (TCM) compounds against epithelial growth factor receptor (EGFR) protein for targeting non-small cell lung cancer (NSCLC). After virtual screening of an initial dataset of 2,242 TCM compounds, leads were identified based on binding energy and ADME/Tox data and subjected to automated docking followed by molecular dynamics simulation. Triptolide, a top compound identified by this vigorous in silico screening, was then tested in vitro on the H2347 cell line carrying wild-type EGFR, revealing an anti-proliferative potency similar to that of known drugs against NSCLC.

No MeSH data available.


Related in: MedlinePlus