IN SILICO STUDY OF CRYO-EM STRUCTURES OF ANTIGEN-ANTIBODY COMPLEX OF CHIKUNGUNYA FOR THE DEVELOPMENT OF DIAGNOSTIC AGENT

Abstract

Objective: Despite the availability of the commercial rapid tests of chikungunya, the difference of pathogen’s genotypes amongst different countries has created some causes for concern. It is found that the sensitivity of the current chikungunya rapid tests on Asian strain was only 20.5%, as compared to 90.3% when tested on the African phylogroup. Therefore, the development of diagnostics that is specific for the current strain circulating in the country is important to be done. The cryo-electron microscopy (cryo-EM) structures of antigen-antibody complex can be used as an insightful structural basis to the development of the tailored antibody for diagnostics purposes. However, cryo-EM structures usually were resolved in low resolution, thus some sterical clashes between residues are expected. This work aims to refine the cryo-EM structures of E1 E2 of chikungunya virus (CHIKV) in complex with antibody using molecular mechanics method, to calculate the binding energy of antigen-antibody complex, and to compare it with the experimental results.Methods: Thecryo-EM structures were refined in vacuoby short minimization scheme using AMBER 14. The binding energies were calculated using Firedock and MM/GBSA methods.Results:The results showed that the direct calculation of binding energies of cryo-EM structures reflected high repulsive forces. While the calculation on the refined structured showed lower binding energies. Visual inspections on the complex structures also indicated that the refined structures showed better interactions.Conclusion:As a conclusion, the refinement of cryo-EM structures should be useful to gain more insight into the binding mode of interactions between antigenic protein and antibody, at the atomic level.