Open AccessPF571 IDENTIFICATION OF HLA‐E AS A KEY GENE IN MULTIPLE MYELOMA BASED ON BIOINFORMATIC ANALYSIS AND DESIGN HIGH‐AFFINITY PEPTIDES TARGETING HLA‐E BASED ON COMPUTATIONAL TECHNIQUES
Author(s) -
Yang Y.,
sun M.,
yu Z.,
Liu Z.,
Wei M.
Publication year - 2019
Publication title -
hemasphere
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 11
ISSN - 2572-9241
DOI - 10.1097/01.hs9.0000560572.18433.9e
Subject(s) - human leukocyte antigen , computational biology , multiple myeloma , gene , protein data bank (rcsb pdb) , protein data bank , gene expression , bone marrow , cancer research , biology , bioinformatics , antigen , immunology , genetics , protein structure , biochemistry
Background: Multiple myeloma (MM) is a common plasma cell malignancy that is currently incurable. Finding potential drug targets and new drugs are crucial for the treatment of thisdisease. Microarray technology is widely used to investigate differential mRNA expression and identify biomarkers in disease, which provides important clues to identifying new treatment targets and then new drugs could be designed. Aims: To find new treatment target for MM and design targeting affinity peptide. Methods: Two datasets (GSE6691 and GSE39754) were obtained from the Gene Expression Omnibus (GEO) database, and a protein‐protein interaction (PPI) network of differentially expressed genes (DEGs) was constructed to identify hub genes.Key clusters in the PPI network were analyzed by Molecular Complex Detection (MCODE). The gene both in hub genes and key clusters could be considered as potential treatment target and will be verified in clinical patients’ bone marrow samples. As the treatment target identified, crystal structure is obtained from Protein Data Bank and affinity peptide drug designed by Molecular Operating Environment (MOE) software. Results: HLA‐E was identified as hub gene and also located in one of the key clusters which could be a potential therapeutic target for MM.The high expression of HLA‐E in myeloma cells was confirmed by measuring HLA‐E mRNA expression in bone marrow samples from MM patients and healthy volunteers from Shengjing Hospital.The crystal structure of HLA‐E from the Protein Data Bank(PDB ID: 3CDG) was used to find the key active area of HLA‐E. MOE softwarewas used to design high‐affinity targeting peptides using key interaction amino acids as model peptides. A peptide library was constructed and screened to identify peptides with the highest stability and affinity for HLA‐E. Three high‐affinity peptides were selected and verified by peptide‐protein docking. Thus, these peptides could serve as targeting heads to find myeloma cells that express high levels of HLA‐E. Summary/Conclusion: HLA‐E could be recognized as a new treatment target for MM. At the meanwhile, affinity peptide(NALDEYCEDKNR) could be considered as a new targeting drug.