1st International and 10th National Iranian Conference on Bioinformatics
Home Accepted Papers
The new approach based on MD studies to design novel anticancer drugs based on amino acids and carbohydrates to inhibit DHFR
Paper ID : 1132-ICB10
Authors:
Amin mohammad Shapouri *, Sepideh Kalhor, Alireza Fattahi
دانشکده شیمی دانشگاه صنعتی شریف
Abstract:
DHFR is one of the essential enzymes in the Thymidylate synthesis cycle. The expression of this enzyme in tumor cells and some related autoimmune diseases such as Psoriasis, which is a derma-related illness, has been observed. The inhibition of this enzyme will lead to suppressing the production of 5,10-Methylenetetrahydrofolate in cells. 5,10-Methylenetetrahydrofolate is produced from tetrahydrofolate with the aid of SHMT. As a result, the mentioned inhibition will cause cell death.[1]
Methotrexate is one of the drugs for treating Psoriasis, which has many side effects such as intestinal problems, respiratory disorders, blood disorders, central nervous system disorders, and elevated liver function.[2]
This project aims to replace Methotrexate with drugs based on carbohydrates and amino acid blocks with fewer side effects.
To achieve our goals in designing new drugs, we employ quantum mechanics and molecular dynamic methods. Firstly, concerning the main drug structure (Methotrexate), some new structures based on amino acids and carbohydrates will be suggested. Then, the newly designed structures will be optimized at the DFT/rB3LYP/6-31G+(d) level. It should be noted that the primary conformer search of the structures will be carried out using Spartan software. Following that, Autodock and Autodock/vina are the software used to select the best replacements. Outputs of the docking procedures will be used for molecular dynamics simulations. Furthermore, the energy analyses for this study will be performed by MM/PBSA method. We hope that the results of this study will lead to the design of more effective and less toxic anticancer and anti-autoimmune drugs.
Keywords:
Inhibitor; Drug design; Computational design; Anti-cancer compounds; Sugar and amino acid; Methotrexate
Status : Paper Accepted (Poster Presentation)