Computational Design and Analysis of a Novel Inhibitor for FERMT1 Gene: A Novel Treatment Strategy for the Kindler Syndrome

Abstract

Epidermolysis Bullosa (EB) is a rare genetic condition characterized by skin blistering that occurs with minimal trauma such as scratching or rubbing. EB is a polygenic disorder caused by various genes, each responsible for different subtypes. This study focuses on Kindler Syndrome, which is caused by mutations in the FERMT1 (FERM Domain Containing Kindlin 1) gene. Currently, topical medications are the primary treatment options due to the lack of suitable drugs. To address this, a computer-aided drug has been designed that could potentially act as an inhibitor for treating Kindler Syndrome. The FERM1 HUMAN protein of FERMT1 was retrieved from the UNIPROT database (with the UNIPROT ID of Q9BQL6) and its secondary and tertiary structure were analyzed using MESSA and AlphaFold 2, respectively. A ligand was then constructed using the Elea3D drug design server and the best ligand, based on the maximum population score, was used to predict and analyze its interaction with the FERMT1 protein using SwissDock. The complex obtained was further subjected to molecular dynamics simulation using IMODs. Finally, ADMET analysis was performed to evaluate the drug-likeness, toxicity, water solubility, and physiochemical properties of the designed drug. Computer-aided drug designed in this study holds potential for treating Kindler Syndrome and may yield exceptional results in in vivo and in vitro studies. Overall, this study demonstrates the potential for using computer-aided drug design to develop new treatments for rare genetic disorders like Kindler Syndrome.