In silico study on the protein-protein interaction of D-dimer and glycoprotein VI in blood plasma as potential biomarker of ischemic stroke

• Main Authors: de Ramos, Brenna R., Ruivivar, Katrina Fatima B.
• Format: text
• Language: English
• Published: Animo Repository 2022
• Subjects: Protein-protein interactions; Glycoproteins; Blood plasma; Physics
• Online Access: https://animorepository.dlsu.edu.ph/etdb_physics/15; https://animorepository.dlsu.edu.ph/context/etdb_physics/article/1020/viewcontent/2022_Ramos_Ruivivar_In_Silico_Study_on_the_Protein_Protein_Interaction_of_D_dimer_Full_text.pdf
• Institution: De La Salle University

This study used an in-silico approach to investigate the molecular interaction between D-dimer and Glycoprotein VI (GPVI) in blood plasma as a potential biomarker for ischemic stroke. GPVI underwent structural validation through Ramachandran Plot, ERRAT, and Verify 3D. Preliminary results showed that GPVI attained a high-quality structural fidelity for molecular docking with high level of accuracy after validation. ClusPro 2.0 was used to dock D-dimer in GPVI whereas Discovery Studio 2021 Client was used to view the interactions between GPVI and D-dimer. It showed that the interactions of the amino acids between the two aforementioned molecules are mostly dominated by intermolecular forces from the Van der Waals and electrostatic forces arising from the hydrogen bonds and hydrophobic bonds. Moreover, to determine the stability of the GPVI - D-dimer bonding, molecular dynamics simulation was undertaken through CABS-Flex 2.0. Visual results with a time step size of 10 nanoseconds showed minimal fluctuations on the receptor-ligand complex with no significant difference (p = 0.54797) between the unbound GPVI and bound GPVI using statistical T-test analysis. Thus, computer simulation has demonstrated that GPVI's structural integrity remained invariant when bounded with D-dimer. This strongly suggests that the stable receptor- ligand complex formed by GPVI, and D-dimer is indicative of a potential biomarker candidate for ischemic stroke in blood plasma. For further in-silico studies, surface plasmon resonance (SPR) can also be considered to validate the results in addition to placing water solvent background in the receptor-ligand complex formed by GPVI and D-dimer.