Abstract
Genome-wide association studies (GWAS) have identified that one of the autoimmune disease-associated loci, predisposing for the development of Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA) and Systemic Sclerosis (SSc), is the rs35677470 missense variant of the Deoxyribonuclease I like 3 (DNASE1L3) gene, leading to R206C substitution in DNASE1L3 enzyme. Molecular Dynamics (MD) simulations were implemented for the wild type and mutated enzyme, in order to investigate the structure-function relationship that leads to partial loss of enzyme function. Results showed loss of salt bridges, larger fluctuation in active site regions and lower charge of the catalytic and DNA binding sites after the mutation. The present study raises the necessity of in silico methods, in understanding and managing autoimmune diseases.
Supplementary Materials
The following are available online at https://www.mdpi.com/article/10.3390/IECBM2022-13378/s1.
Author Contributions
Conceptualization, A.A., and T.T.; visualization, M.S., A.A., E.C.; methodology and validation, formal analysis, investigation, data curation, M.S., A.A., E.C., T.T.; writing—original draft preparation, writing—review and editing, A.A., E.C., T.T.; supervision, T.T. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
The data presented in this study are available on request from the corresponding author.
Acknowledgments
We acknowledge support of this work by the project “INSPIRED—The National Research Infrastructures on Integrated Structural Biology, Drug Screening Efforts and Drug Target Functional Characterization” (Grant MIS 5002550), which is implemented under the Action “Reinforcement of the Research and Innovation Infrastructure”, funded by the Operational Programme “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014–2020) and co-financed by Greece and the European Union (European Regional Development Fund). Authors are grateful to Elias Eliopoulos for fruitful discussion and assistance throughout all aspects of our study, Kostas Bethanis and George Goulielmos for suggestions and discussion.
Conflicts of Interest
The authors declare no conflict of interest.
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