Discovery of direct inhibitor of KRAS oncogenic protein by natural products: a combination of pharmacophore search, molecular docking, and molecular dynamic studies.

ABSTRACT:

Background and purpose

Aberrant signaling by oncogenic RAS proteins occurs in almost all human tumors. One of the promising strategies to overcome such cancers is the inhibition of KRAS protein, a subtype of RAS family involved in cell growth, differentiation, and apoptosis, through preventing its effector, SOS1, from being attached to the protein.

Experimntal approach

Herein, a virtual screening process was performed using pharmacophore search, molecular docking, and molecular dynamic simulations. A pharmacophore model was created to indicate essential features for a KRAS inhibitor and used for screening the National Cancer Institution (NCI) database to retrieve similar compounds to the pharmacophore model with more than 70% similarity. Chosen compounds were then docked int

SUBMITTER: Hashemi S 

PROVIDER: S-EPMC7540812 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature