Assessment of Novel Proteins Triggering Celiac Disease via Docking-Based Approach
Human leukocyte antigens (HLAs) are pivotal in antigen processing, presenting to CD4+ T cells, and are linked to autoimmune disease susceptibility. In celiac disease, HLA-DQ2.5 and HLA-DQ8.1 bind gluten peptides on APCs, some recognized by CD4+ T cells, prompting inflammation and tissue damage. Whil...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/29/1/138 |
| _version_ | 1827384640874217472 |
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| author | Mariyana Atanasova Ivan Dimitrov Antonio Fernandez Javier Moreno Frits Koning Irini Doytchinova |
| author_facet | Mariyana Atanasova Ivan Dimitrov Antonio Fernandez Javier Moreno Frits Koning Irini Doytchinova |
| author_sort | Mariyana Atanasova |
| collection | DOAJ |
| description | Human leukocyte antigens (HLAs) are pivotal in antigen processing, presenting to CD4+ T cells, and are linked to autoimmune disease susceptibility. In celiac disease, HLA-DQ2.5 and HLA-DQ8.1 bind gluten peptides on APCs, some recognized by CD4+ T cells, prompting inflammation and tissue damage. While extensively studied experimentally, these alleles lack comprehensive in silico analysis. To explore peptide–HLA preferences, we used molecular docking on peptide libraries, deriving quantitative matrices (QMs) for evaluating amino acids at nine-residue peptide binding cores. Our findings tie specific residue preferences to peptide backbone conformations. Validating QMs on known binders and non-binders showed strong predictive power (89–94% accuracy). These QMs excel in screening protein libraries, even whole proteomes, notably reducing time and costs for celiac disease risk assessment in novel proteins. This computational approach aligns with European Food Safety Authority guidance, promising efficient screening for potential celiac disease triggers. |
| first_indexed | 2024-03-08T15:01:57Z |
| format | Article |
| id | doaj.art-f46cbfc366db42c6ae22a18890e7c8cc |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-08T15:01:57Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-f46cbfc366db42c6ae22a18890e7c8cc2024-01-10T15:04:17ZengMDPI AGMolecules1420-30492023-12-0129113810.3390/molecules29010138Assessment of Novel Proteins Triggering Celiac Disease via Docking-Based ApproachMariyana Atanasova0Ivan Dimitrov1Antonio Fernandez2Javier Moreno3Frits Koning4Irini Doytchinova5Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaFaculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaEuropean Food Safety Authority, 43126 Parma, ItalyInstituto de Investigación en Ciencias de la Alimentación (CIAL), Consejo Superior de Investigaciones Cientificas-Universidad Autonoma de Madrid (CSIC-UAM), Campus of Interntional Excellence—CEI (UAM+CSIC), Nicolás Cabrera, 9, 28049 Madrid, SpainDepartment of Immunohematology and Blood Transfusion, Leiden University Medical Centre, 2333 ZA Leiden, The NetherlandsFaculty of Pharmacy, Medical University of Sofia, 1000 Sofia, BulgariaHuman leukocyte antigens (HLAs) are pivotal in antigen processing, presenting to CD4+ T cells, and are linked to autoimmune disease susceptibility. In celiac disease, HLA-DQ2.5 and HLA-DQ8.1 bind gluten peptides on APCs, some recognized by CD4+ T cells, prompting inflammation and tissue damage. While extensively studied experimentally, these alleles lack comprehensive in silico analysis. To explore peptide–HLA preferences, we used molecular docking on peptide libraries, deriving quantitative matrices (QMs) for evaluating amino acids at nine-residue peptide binding cores. Our findings tie specific residue preferences to peptide backbone conformations. Validating QMs on known binders and non-binders showed strong predictive power (89–94% accuracy). These QMs excel in screening protein libraries, even whole proteomes, notably reducing time and costs for celiac disease risk assessment in novel proteins. This computational approach aligns with European Food Safety Authority guidance, promising efficient screening for potential celiac disease triggers.https://www.mdpi.com/1420-3049/29/1/138celiac diseaseHLA-DQ2.5HLA-DQ8.1molecular dockingquantitative matrixpeptide binding prediction |
| spellingShingle | Mariyana Atanasova Ivan Dimitrov Antonio Fernandez Javier Moreno Frits Koning Irini Doytchinova Assessment of Novel Proteins Triggering Celiac Disease via Docking-Based Approach Molecules celiac disease HLA-DQ2.5 HLA-DQ8.1 molecular docking quantitative matrix peptide binding prediction |
| title | Assessment of Novel Proteins Triggering Celiac Disease via Docking-Based Approach |
| title_full | Assessment of Novel Proteins Triggering Celiac Disease via Docking-Based Approach |
| title_fullStr | Assessment of Novel Proteins Triggering Celiac Disease via Docking-Based Approach |
| title_full_unstemmed | Assessment of Novel Proteins Triggering Celiac Disease via Docking-Based Approach |
| title_short | Assessment of Novel Proteins Triggering Celiac Disease via Docking-Based Approach |
| title_sort | assessment of novel proteins triggering celiac disease via docking based approach |
| topic | celiac disease HLA-DQ2.5 HLA-DQ8.1 molecular docking quantitative matrix peptide binding prediction |
| url | https://www.mdpi.com/1420-3049/29/1/138 |
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