Computer-Aided Drug Design Boosts RAS Inhibitor Discovery

The Rat Sarcoma (RAS) family (NRAS, HRAS, and KRAS) is endowed with GTPase activity to regulate various signaling pathways in ubiquitous animal cells. As proto-oncogenes, RAS mutations can maintain activation, leading to the growth and proliferation of abnormal cells and the development of a variety...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2022-09, Vol.27 (17), p.5710
Main Authors: Wang, Ge, Bai, Yuhao, Cui, Jiarui, Zong, Zirui, Gao, Yuan, Zheng, Zhen
Format: Article
Language:English
Subjects:
Amino acids
Animals
Binding sites
Cancer
Cell cycle
Cell growth
Cell proliferation
Chemical inhibitors
Computational Biology
Computer applications
Computer-Aided Design
computer-aided drug design
Design
Drug Design
Drug development
Drug discovery
Drugs
Epidermal growth factor
Humans
Inhibitors
Kinases
Ligands
molecular docking
molecular dynamics simulation
Mutation
Neoplasms - pathology
Phosphorylation
Product development
Proteins
Proteins - chemistry
Proto-oncogenes
RAS inhibitor
Ras protein
Review
Sarcoma
Signal transduction
Technology application
Toxicity
Tumors
virtual screening
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Summary:The Rat Sarcoma (RAS) family (NRAS, HRAS, and KRAS) is endowed with GTPase activity to regulate various signaling pathways in ubiquitous animal cells. As proto-oncogenes, RAS mutations can maintain activation, leading to the growth and proliferation of abnormal cells and the development of a variety of human cancers. For the fight against tumors, the discovery of RAS-targeted drugs is of high significance. On the one hand, the structural properties of the RAS protein make it difficult to find inhibitors specifically targeted to it. On the other hand, targeting other molecules in the RAS signaling pathway often leads to severe tissue toxicities due to the lack of disease specificity. However, computer-aided drug design (CADD) can help solve the above problems. As an interdisciplinary approach that combines computational biology with medicinal chemistry, CADD has brought a variety of advances and numerous benefits to drug design, such as the rapid identification of new targets and discovery of new drugs. Based on an overview of RAS features and the history of inhibitor discovery, this review provides insight into the application of mainstream CADD methods to RAS drug design.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules27175710