Abstract B2-44: Structure-based design of inhibitory peptides for LRP6

Abstract

Abstract Wnt signaling pathway plays a major role in regulation of cell proliferation, migration, tissue homeostasis, tumor progression and cancer. This pathway can be antagonized by DKK proteins, which disrupt the intiationary complex (Frizzled-LRP5/6 complex). Nowadays, use of peptides in order to target tumor cells is attracting much attention. In this study, a computational protocol is presented to structural design of inhibitory peptides aginst Low-density lipoprotein receptor-related protein 6 (LRP6) as receptor. Firstly, natural ligand of LRP6 divided to 12 fragments as peptide derivatives. Then, molecular dynamics simulations used for structural energy minimization by means of Gromacs 4.5.4. The binding affinities of designed peptides were investigated via molecular docking using ClusPro webTool. Finally, stability and binding free energy of peptides were calculated by FoldX software. The results showed that four of designed peptides had the highest affinity to interact with the receptor and can be considered as candidates for inhibition of wnt signaling pathway through LRP5/6 receptor. Citation Format: Elham Rismani, Hamzeh Rahimi, Kayhan Azadmanesh, Shahriar Arab, Morteza Karimipoor, Ladan Teimoori-Toolabi. Structure-based design of inhibitory peptides for LRP6. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B2-44.