Antibody-Mediated Detection of Claudin-5 as a Biomarker Associated with Suicidal Behavior

Claudin 5 is a protein in the blood-brain barrier (BBB) tight junction. Recently, its breakdown has been linked to a biomarker for suicide. The presence of Claudin 5 in blood could be an indicator that could pre- dict or diagnose the risk of suicide. Antibodies are specialized proteins that bind to foreign substances, bacteria, viruses, or toxins. We hypothesize that Claudin 5 has a specific region on its surface to which an- tibodies can bind, serving as a detection tool. In the current study, we performed computational modeling simulations to identify antibodies that can strongly bind to the Claudin 5 protein. Specifically, we first modeled the 3D structure of the Claudin 5 protein using AlphaFold 3, and nine antibodies were down- loaded from the Protein Data Bank (PDB). These nine antibodies were separately docked on Claudin      5 protein to form Claudin 5-antibody complex utilizing the HDOCK2.0 software. The output from the HDOCK software was downloaded and were analyzed. Claudin 5-antibody complexes were primarily visually and analyzed to ensure that the antibody binds to the binding site predicted by the graph neural network by using the GrASP web server. Secondly, the binding energy between Claudin 5 and antibod- ies was calculated using the PRODIGY software, and finally, hydrogen bonds were determined using an in-house script. Based on the above analysis, Antibody IX showed the most suitable binding and could be used for detecting Claudin-5. The current investigation could lead to new diagnostic tools that help in early detection and intervention and could potentially save lives from suicide.