Computational Targeting Of Rhoh Gtpase: An In Silico Drug Discovery Strategy Against Cancer Progression

Abstract

RhoH is an atypical Rho GTPase with restricted expression in hematopoietic cells and lacks intrinsic GTPase activity [1]. Although it regulates T-cell receptor signaling [2], recent studies link RhoH to tumour-related mechanisms such as immune evasion [3], enhanced survival [4], and metastasis [5] through P13K-Akt [6], NF- B [7], and Rac1-JNK pathways [8]. To explore its therapeutic potential, we constructed a 3D homology model of RhoH and validated it structurally. Docking simulations revealed interactions with Rac1, ZAP-70 [9], and drug-like ligands, identifying key binding residues. This study provides new structural insights into RhoH and supports its role as a candidate for targeted cancer therapy development.