Identification of Novel Src Inhibitors: Pharmacophore-Based Virtual Screening, Molecular Docking and Molecular Dynamics Simulations
Copyright policy )Identification of Novel Src Inhibitors: Pharmacophore-Based Virtual Screening, Molecular Docking and Molecular Dynamics Simulations
Src plays a crucial role in many signaling pathways and contributes to a variety of cancers. Therefore, Src has long been considered an attractive drug target in oncology. However, the development of Src inhibitors with selectivity and novelty has been challenging. In the present study, pharmacophore-based virtual screening and molecular docking were carried out to identify potential Src inhibitors. A total of 891 molecules were obtained after pharmacophore-based virtual screening, and 10 molecules with high docking scores and strong interactions were selected as potential active molecules for further study. Absorption, distribution, metabolism, elimination and toxicity (ADMET) property evaluation was used to ascertain the drug-like properties of the obtained molecules. The proposed inhibitor–protein complexes were further subjected to molecular dynamics (MD) simulations involving root-mean-square deviation and root-mean-square fluctuation to explore the binding mode stability inside active pockets. Finally, two molecules (ZINC3214460 and ZINC1380384) were obtained as potential lead compounds against Src kinase. All these analyses provide a reference for the further development of novel Src inhibitors.
- China Medical University China (People's Republic of)
Databases, Pharmaceutical, Drug Evaluation, Preclinical, Molecular Conformation, Organic chemistry, Quantitative Structure-Activity Relationship, Src inhibitors, Molecular Dynamics Simulation, Ligands, Article, QD241-441, Drug Discovery, Humans, Protein Interaction Domains and Motifs, Protein Kinase Inhibitors, Binding Sites, pharmacophore model, Molecular Structure, Reproducibility of Results, molecular docking, molecular dynamics simulations, virtual screening, Molecular Docking Simulation, src-Family Kinases, Protein Binding
Databases, Pharmaceutical, Drug Evaluation, Preclinical, Molecular Conformation, Organic chemistry, Quantitative Structure-Activity Relationship, Src inhibitors, Molecular Dynamics Simulation, Ligands, Article, QD241-441, Drug Discovery, Humans, Protein Interaction Domains and Motifs, Protein Kinase Inhibitors, Binding Sites, pharmacophore model, Molecular Structure, Reproducibility of Results, molecular docking, molecular dynamics simulations, virtual screening, Molecular Docking Simulation, src-Family Kinases, Protein Binding
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).37 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!