Ras, from "Rat sarcoma virus", is a family of related proteins that are expressed in all animal cell lineages and organs.

When Ras is 'switched on' by incoming signals, it subsequently switches on other proteins, which ultimately turn on genes involved in cell growth, differentiation, and survival.

[3] In 1982, activated and transforming human ras genes were discovered in human cancer cells by Geoffrey M. Cooper at Harvard,[7] Mariano Barbacid and Stuart A. Aaronson at the NIH,[8] Robert Weinberg at MIT,[9] and Michael Wigler at Cold Spring Harbor Laboratory.

The three human ras genes encode extremely similar proteins made up of chains of 188 to 189 amino acids.

The G2 motif, also called Switch I or SW1, contains threonine35, which binds the terminal phosphate (γ-phosphate) of GTP and the divalent magnesium ion bound in the active site.

The D is aspartate57, which is specific for guanine versus adenine binding, and Q is glutamine61, the crucial residue that activates a catalytic water molecule for hydrolysis of GTP to GDP.

Ras proteins function as binary molecular switches that control intracellular signaling networks.

Ras and Ras-related proteins are often deregulated in cancers, leading to increased invasion and metastasis, and decreased apoptosis.

Ras activates several pathways, of which the mitogen-activated protein (MAP) kinase cascade has been well-studied.

This cascade transmits signals downstream and results in the transcription of genes involved in cell growth and division.

As per its classification, Ras has an intrinsic GTPase activity, which means that the protein on its own will hydrolyze a bound GTP molecule into GDP.

However this process is too slow for efficient function, and hence the GAP for Ras, RasGAP, may bind to and stabilize the catalytic machinery of Ras, supplying additional catalytic residues ("arginine finger") such that a water molecule is optimally positioned for nucleophilic attack on the gamma-phosphate of GTP.

They insert close to the P-loop and magnesium cation binding site and inhibit the interaction of these with the gamma phosphate anion.

In the GTP-bound conformation, Ras has a high affinity for numerous effectors which allow it to carry out its functions.

These function by slowing the exchange of GDP for GTP, thus prolonging the inactive state of Ras family members.

NRAS and HRAS are further processed on the surface of the Golgi apparatus by palmitoylation of one or two Cys residues, respectively, adjacent to the CaaX box.

The clinically most notable members of the Ras subfamily are HRAS, KRAS and NRAS, mainly for being implicated in many types of cancer.

Mutations in the Ras family of proto-oncogenes (comprising H-Ras, N-Ras and K-Ras) are very common, being found in 20% to 30% of all human tumors.

[20] It is reasonable to speculate that a pharmacological approach that curtails Ras activity may represent a possible method to inhibit certain cancer types.

[22] Ras inhibitor trans-farnesylthiosalicylic acid (FTS, Salirasib) exhibits profound anti-oncogenic effects in many cancer cell lines.

[23][24] Inappropriate activation of the gene has been shown to play a key role in improper signal transduction, proliferation and malignant transformation.

[citation needed] The tumour suppressor gene NF1 encodes a Ras-GAP – its mutation in neurofibromatosis will mean that Ras is less likely to be inactivated.

The novel strategy proposes finding small glue molecules, which attach the mutated Ras to the GAP, prohibiting uncontrolled cell growth and restoring the normal function.

For this goal a theoretical Ras-GAP conformation was designed with a several Å gap between the molecules, and a high-throughput in silico docking was performed for finding gluing agents.

This is evidenced by severe developmental failure in deficient ras expression and by significant impairment of various life activities when artificially expressed, such as: increased concentration of inositol phosphates; likely reduction of cAMP binding to chemotaxis receptors; and that is likely the reason cGMP synthesis is impaired.