The simplest solution is construction of scaffold proteins - if you know contact sequences of RAS and ROK then use that sequences to inhibit contact. For example, if you know that RAS seuence (hypothetical) at position 5-12 is contacting ROK seuence (hypothetical) 65-65, than synthetise and add them (only one in one experiment) to culture, with or without carrier which enables delivery. Short peptides are surprisingly good in penetrating to different parts of cell. Partial RAS sequence will bind to ROK, and prevent binding of full RAS molecule.

Of course, this is very simplified version - you will need help of someone with good knowledge of protein-protein interactions and peptide delivery to cells.

Kind regards,

Paško

You can try coating drugs inhibiting RAS-RAF for better tumor delivery instead of peptides

Dear Neda,

Nice to meet you!

As you know, Ras protein and Ras superfamily mediate membrane association and serve as lipid anchors. So their functions are limited to the cytoplasmic side of the cell membrane, where they receive specific signals and transmit them further.

Thus, if you are going to design a Ras inhibitor peptide and corresponding nano-delivery system, first of all it must be able to penetrate the target cells! and this requires the drug and/or delivery system be actively targeted to the cancer cells. There are good tumor penetrating peptides and motifs serving also as receptor targeting ligands...

In respect of the delivery system, there are different options: Liposomes, Polymeric nanoparticles, dendrimers, targeted drug conjugates, etc. Selection depends on the research purpose and design.. I'm myself working on PLGA-b-PEG copolymer nanoparticles.

Regarding the peptide design, you should do some bioinformatics stuff, modeling and protein-protein docking. You also may go through "phage display technology" to select a specific peptide instead of de novo design. However, first of all you need to determine your very target. You may target Ras protein directly and design a peptide that specifically binds to and triggers conformational changes in "inactive Ras" (GDP-state-Ras), so that the protein is inhibited from activation; Or you may design a peptide that specifically binds to GEF(Guanine nucleotide exchange factor) which is the activator of Ras, and hence prevents from Ras activation(converting to GTP-state-Ras). 

Any way, I wish you success dear compatriot !

Sincerely,

Farzad.

SATPdb: a database of structurally annotated therepeutic peptides.

http://crdd.osdd.net/raghava/satpdb/

paper link

http://nar.oxfordjournals.org/content/early/2015/11/01/nar.gkv1114.full