(451i) Exploring the Relationship Between Helicobacter Pylori's Caga Sequence and Affinity with Host's Receptors: A Proposal for Molecular Diagnostic Tools

Helicobacter pylori is a human pathogen reported to be present in nearly 50% of world’s population^1,2. Moreover the virulence of the strain is one of the major determinants for disease developing among infected people. One of the major factors associated to H. pylori virulence is the cytotoxin associated gene A (cagA) which encodes the CagA protein^3,4. This protein is injected directly from the microorganism through type 4 secretion system (T4SS) to gastrointestinal epithelial cells, where disrupts the cellular signaling mechanism⁵. It is known that CagA has a 5’ region highly conserve while 3’ region is variable due to the presence of different types and/or numbers of repeat sequences which contains an EPIYA motif location where the phosphorylation of the protein takes place^2,6. These differences in sequence may have a relationship with the affinity of CagA with host’s receptors and hence with the pathogenicity of H. pylori. Here in this work we obtained several sequences of different Colombian CagA strains and determine the tertiary structure using I-Tasser⁷ server based on multiple threading complemented with Replica Exchange Dynamics technique⁸ using opportunistic Cloud Infraestructure. Then, these structures were docked^9,10 with different receptors including SCHP-2 and Src. Free energy calculations were correlated with the pathogenicity of the strains which were previously categorized by its pathogenicity level (cancer, chronic ulcer, chronic gastritis etc) in order to determine a potential tool for molecular diagnostics.

References

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8.        Sugita Y, Okamoto Y. Replica-exchange molecular dynamics method for protein folding. Chemical Physics Letters. 1999;314(1-2):141-151.

9.        Qu K, Brooijmans N. Structure-Based Drug Design Computational Methods for Protein Structure Prediction and Modeling. In: Xu Y, Xu D, Liang J, eds: Springer New York; 2007:135-176.

10.      Pierce B, Weng Z. Structure prediction of protein complexes. Computational methods for protein structure prediction and modeling. 2007:109-134.