1st International and 10th National Iranian Conference on Bioinformatics
Home Accepted Papers
Binder design for targeting SARS-CoV-2 spike protein: An in silico perspective
Paper ID : 1281-ICB10
Authors:
Ali Etemadi1, Hamid Reza Moradi *2, Farideh Mohammadian3, Mohammad Hossein Karimi Jafari4, Babak Negahdari1, Yazdan Asgari5, MohammadAli Mazloomi1
1Medical Biotechnology Department, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran
2Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
3Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz,
4Department of Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
5Medical Biotechnology Department, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences (TUMS), Tehran,Iran
Abstract:
The COVID-19 pandemic is affecting all aspects of people lives around the world. Coronaviruses are single-stranded RNA viruses and SARS-CoV2 belongs to the second group of this family[1]⁠. Spike glycoprotein (S protein) of the virus is the key molecule employed for cell penetration by binding to the receptor-binding domain (RBD) of angiotensin converting enzyme 2(ACE2). It is the only homing receptor recognized for the virus till date[2]⁠. Blocking the Interaction of S protein and ACE2 can inhibit the virus from entering the cell and replication. Small Proteins (2 – 20 kDa) as antiviral medications, may hold great promises as the future of therapeutics. Owing to the advances in the field of structural biology, it is now possible to design, highly selective small proteins. Here, we aimed at designing some novel binders to block the S protein of the SARS-CoV2.


The design process was based on collecting a list of natural proteins from PDB database[3]⁠. Collected proteins were monomeric, expressed in E.Coli and had no RNA, DNA, ligand or mutation in their structure. Then an Initial directed docking was performed by Patchdock against SARS-CoV2 S protein. Best performing protein was selected (3HGL) and used for interface designing by Rosettas FastDesign[4]⁠. Next the new designed models were filtered and Cluspro and PatchDock was used for blind docking to select the best binders[5,6]⁠. Also their structural parameters and characteristics was assessed with different web based tools. In the end, according to the data gathered from previous step three best performing binders have been chosen (BIN32,BIN78,BIN91). In order to investigate the conformational behavior of the binder's models and native scaffold, MD simulation was used[7]⁠. The results showed that BIN32,BIN78,BIN91 have a high binding energy towards S proteins of the SARS-CoV2. (-22.43, -20.91 and -17.01 kcal/mol respectively)
Keywords:
Protein design, COVID-19, Rosetta , MD simulations, Small Proteins
Status : Paper Accepted (Poster Presentation)