Abstract 3694: Molecular modeling studies of novel receptor targeted peptides in the treatment of prostate cancer
Authors: Abdalla Mohamed O. , Bin Salam Ahmad , Hembrick Vincent , Bhavaraju Manikanthan , Yates Clayton , Jaynes Jesse , Turner Timothy 
Published: August 2015

Abstract
Purpose: Prostate Cancer (PCa) is the second leading cause of cancer-related deaths among men in the United States. Due to the harsh side effects of conventional chemo- and radio-therapies, targeted drug delivery is now gaining focus of cancer researchers. The key for success for any newly developed targeted drug delivery systems is the novel design of targeting peptides which have high binding affinities to differentially over-expressed receptors on the surface of PCa cells. Four over-expressed receptors which can be targeted on the cell surface of PCa cells are: (GnRH), (EGFR), (PSMA), and (uPAR). Thus, we propose to study the binding affinity of tweleve novel designed targeting peptides (three peptides per receptor) for these over-expressed receptors. Initially, we will study the binding affinity using a computerized molecular modeling program. We will corroborate our modeling data by determining the dissociation constants of the peptide-receptor interaction using sensitive experimental tools such as miscroscale thermophoresis.
Methods: The newly designed peptides were generated in pdb (protein database) format and the known pdb files of the receptors were collected from protein data bank. Cluspro 2.0, developed by Boston University, is a protein docking server with a molecular modeling program that was used to calculate the binding energies of these peptides to their corresponding receptors. The data obtained was analyzed using Pymol. Results: The molecular docking studies showed that the GnRH tarteting peptide QH10, uPAR targeting peptide CV13, EGFR targeting peptide RL10, and PSMA targeting peptide TH12 have the lowest mean binding energies for their respective top three binding conformations. The calculatd binding energies for the aftermentioed peptides-receptors combination are: -1285 KCal/M, -1029 KCal/M, -1019 KCal/M and -1037 KCal/M, respectively. There results suggested a very high interaction for these newly designed peptides and their corroponding receptors as the typical calculated binding energy for an antigen-antibody interaction is -700 KCal/M.
Conclusion: Based on our molecular docking studies, we have determined the best targeting peptides among all the newly desiged peptides. The binding efficiency of the targeting peptides with the lowest binding energies will be further investigated using microscale thermophoresis.
This work is supported by grant funding from NIH/RCMI G12MD00758 (T. Turner) and NIH/NCI U54 CA118623 (T. Turner & M. Abdalla).
Note: This abstract was not presented at the meeting.
Citation Format: Mohamed O. Abdalla, Ahmad Bin Salam, Vincent Hembrick, Manikanthan Bhavaraju, Clayton Yates, Jesse Jaynes, Timothy Turner. Molecular modeling studies of novel receptor targeted peptides in the treatment of prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3694. doi:10.1158/1538-7445.AM2015-3694