IN SILICO EXPLORATION FOR REPURPOSING BREAST CANCER MEDICATIONS IN SLEEP AND NEURODEVELOPMENTAL DISORDERS

Abstract

Sleep is crucial neurobiological behavior that serves a significant part in maintaining brain homeostasis and functioning. It is controlled by two main mechanisms: Homeostatic regulation, which involves the accumulation and dissipation of sleep pressure based on prior wakefulness, and Circadian regulation, which follows a 24-hour cycle synchronized with environmental cues. This article employs bioinformatics software and utilizes databases commonly used in computer science and biology to investigate the potential interaction between CRY1, CLOCK, and PER1/PER2 in drug binding. CRY1 (Cryptochrome 1) and PER1/PER2 (Period 1 and Period 2) are genes involved in the molecular circadian clock. Understanding their interaction and potential drug binding can provide valuable insights into the molecular mechanisms underlying sleep regulation. The bioinformatics software and databases aid in predicting and analyzing the structural and functional aspects of CRY1, CLOCK, and PER1/PER2 interactions. By utilizing computational approaches, this research aims to uncover potential binding sites, identify key residues involved in the interaction, and predict the binding affinity between drugs and these proteins. By exploring the drug-binding potential of CRY1, CLOCK, and PER1/PER2, this study seeks to contribute to understanding the intricate molecular processes underlying sleep regulation. The findings have the potential to inform the development of targeted therapeutics and interventions aimed at modulating sleep patterns and addressing sleep-related disorders. vi Cyto Hubba, Bio via, Open babel, Drug bank, Avogadro, Auto dock, PyRx, and Protein protein interaction clustering String are several computational techniques implemented in the investigation. The CRY1/CRY2 cytochrome genes are crucial for the circadian rhythm. CRY1 is a stronger repressor of clock: BMAL1 as compared to CRY2. It has been recently discovered CRY1 by creating a transcriptional inhibitor enhances its repressive function that results from the lengthening of Circadian rhythm in humans. The Association of PER2 with CRY2 forms a stable complex with CLOCK: BMAL1 whereas in the case of CRY1, there is no need for PER1/PER2 to bind with CLOCK: BMAL1. Methylation in PER1/PER2 promoter is one of the variables that increase the chance of breast cancer. Trastuzumab is used for the treatment of breast cancer by repairing cell division and repair. The present investigation used Molecular Docking of Trastuzumab as a control to analyze the interaction between CRY1 and PER1/PER2 applying Cyto Hubba as well as PPI clustering relationships or other breast cancer FDA approved drugs i.e., (Dichloroplatinum, Anastrozole, Exemestane, Fluvestrant, Lapatinib Ditosylate, Letrozole, Olaparib, Palbociclib, and Talazoparib Tosylate) and Circadian clock protein complex. Exemestane can be seen as a possible medication to treat sleep disturbances because of its highest binding energy as compared to others. The results suggest that Exemestane and Circadian clock protein complex laboratory trials determine its inhibitory potential on CLOCK to minimize sleep problems.