Maulik, U. | bioRxiv Science

bioRxiv2020

Strategies for vaccine design for corona virus using Immunoinformatics techniques

The cutting-edge technology vaccinomics is the combination of two topics immunogenetics and immunogenomics with the knowledge of systems biology and immune profiling for designing vaccine against infectious disease. In our present study, an epitope-based peptide vaccine against nonstructural protein 4 of beta coronavirus, using a combination of B cell and T cell epitope predictions, followed by molecular docking methods are performed. Here, protein sequences of homologous nonstructural protein 4 of beta coronavirus are collected and conserved regions present in them are investigated via phylogenetic study to determine the most immunogenic part of protein. From the identified region of the target protein, the peptide sequence IRNTTNPSAR from the region ranging from 38-47 and the sequence PTDTYTSVYLGKFRG from the positions of 76-90 are considered as the most potential B cell and T cell epitopes respectively. Furthermore, this predicted T cell epitopes PTDTYTSVY and PTDTYTSVYLGKFRG interacted with MHC allelic proteins HLA-A*01:01 and HLA-DRB5*01:01 respectively with the low IC50 values. These epitopes are perfectly fitted into the epitope binding grooves of alpha helix of MHC I molecule and MHC II molecule with binding energy scores -725.0 Kcal/mole and -786.0 Kcal/mole respectively, showing stability in MHC molecules binding. This MHC restricted epitope PTDTYTSVY also showed a good conservancy of 50.16% in world population coverage. This MHC I HLA-A*01:01 allele is present among 58.87% of Chinese population also. Therefore, the epitopes IRNTTNPSAR and PTDTYTSVYLGKFRG may be considered as potential peptides for peptide-based vaccine for coronavirus after further experimental study.

immunology↗

bioRxiv2019

Studying POU2F1 to Unveil the Structural Facet for Pan-Cancer Analysis Considering the Functional Annotations and Sequence-Structure Space Paradigm

POU domain class 2 homebox 1 (POU2F1) is largely known for its transcription factor(TF) activity. Due to its association with different types of malignancies, POU2F1 becomes one of the key factors in pan-cancer analysis. However, in spite of understanding it as a potential drug target, none of the drug has been designed till date due to its extreme dynamicity. In this article, we have proposed a three fold comprehensive framework for understanding the structural conservation and co-variation of POU2F1. Firstly, a gene regulatory network based non-pathogenic and pathogenic study have been performed to understand the strong association between cancers and POU2F1. After that, based on evolutionary sequence space study, the comparative sequential dynamicity of the protein members of POU domain family has been observed mostly between non-human and human samples. Subsequently, the reciprocity effect of the residual co-variation has been identified through direct coupling analysis. Along with that, the structure of POU2F1 has been analysed depending on quality assessment and normal mode based structure network. Comparing the sequence and structure space information, the most significant set of residue viz., 3, 9, 13, 17, 20, 21, 28, 35, 36 have been identified as structural facet for stable binding. It is observed that targeting these residues can help to prevent the monomeric aggregations. This study demonstrates-the observed malleability of POU2F1 is one of the prime reason behind its functional multiplicity in terms of protein moonlighting.\n\nSIGNIFICANCEPOU2F1 is one of the important TFs associated with several malignancies. In spite of orderly stable structure in primitive family proteins, this protein is highly unstable at the monomeric stage. Previous studies show that POU2F1 has a clear association with 121 different diseases. Therefore, it becomes one of the important links in the pan-cancer study. Interestingly, TFs can be considered as a potential drug target. However, it is hardly possible to control the extreme dynamicity of TFs. In this regard, protein moonlighting plays an important role. We have tried to provide a theoretical frame to build understanding on POU2F1. The study provides pathogenic and non-pathogenic connections of the protein in terms of comprehensive and precise Gene Regulatory Network. Subsequently, the instability has been unveiled and the structural facet has been identified. Finally, the specified set of function for a suitable session to target the protein is analyzed based on protein moonlighting properties.

bioinformatics↗