A Review of the in Silico Design and Development Approaches of Ras-Specific Anticancer Therapeutics

Abstract

Ras Proteins, play a pivotal role in the proliferation pathways, and Ras mutant forms are well-established cancer drivers. Ras mutations are found in about 30% of all human cancers widely known as challenging diseases to control and treat. The direct inhibition of Ras is challenging and makes Ras an “undruggable” target for many years. The important reason is, that Ras protein has a unique smooth surface and shows different dynamicity upon binding GDP and GTP. As a result, interfering peptides (IPs) targeting the Ras family protein-protein interactions (PPIs) are considered more likely to bind Ras effectively and inhibit the downstream signaling. In this review, we aimed to cover the recent approaches to design the peptides that target Ras family proteins, focusing on in silico methods. In this regard, the anti-cancer peptide development approaches including design and delivery strategies are discussed. Later, more specific methods regarding Ras-specific peptide design are presented. In conclusion, IPs are a promising group of cancer therapeutics to combat Ras mutant cancers. For future perspectives to have these peptides in clinical use, co-inhibition of other cancer targets as well as improving the pharmacokinetic features of peptides are suggested.