| dc.description.abstract | Cancer has significant treatment challenges including drug resistance and lack of specific treatment with minimal side effects. Peptide-based therapy is a new strategy in cancer treatment that has advantages such as short sequence, easy synthesis and modification, biocompatibility, specific targeting, and low inherent toxicity, which make them promising as anticancer therapeutics. Although the anticancer mechanism of ACPs is not thoroughly understood, they can be divided into four groups based on their activity, with anti-angiogenic effects, immune system regulation, cell membrane disruption, and apoptosis induction. In the first step of this study, ApInAPDB (Apoptosis-Inducing Anticancer Peptides Database) was developed and introduced as a comprehensive database for apoptosis-inducing anticancer peptides. In the next step, the BIM sequence was determined as a Lead peptide by screening using the ApInAPDB database and alignment with PRALINE software. As potential anticancer agents, BIM-derived peptides can target overexpressed anti-apoptotic proteins such as Mcl-1 in cancer cells and induce apoptosis. The effect of helicity and hydrophilicity on their functionality has been raised as the most important challenge in the design of peptides derived from BIM. At first, contact finder web server software was used to determine BIM amino acids involved in the Mcl-1 complex, and all amino acids that are highly related to the surface receptor, identified to remain unchanged in the design process to maintain the performance of analogs. After designing analogs, their secondary structures were predicted by Cham Finder web server software and GOR, Neural Network, and Chou-Fasman algorithms, and from the GRAVY values of -0.98 and -1.85 for BIM (LP) and analog 5 respectively, it can be concluded that analog 5 is more hydrophilic than BIM (LP). In the nano-scale modeling stage, molecular dynamics simulation was performed for 100 nanoseconds using GROMACS software, with the CHARMM36 force field, then MM-PBSA calculations were also performed to evaluate the affinity of binding to Mcl-1 and Bcl-xL receptors, which showed that the analog 5 with -95.91 kJ.mol-1 has the best binding energy to Mcl-1. In vitro evaluations confirmed that analog 5, | en_US |
