Exploring the binding potential of natural compounds to carbonic anhydrase of cyanobacteria through computer-based simulations

Cyanobacteria in water bodies cause harmful cyanobacterial blooms, releasing toxins that degrade water quality and cause health issues. Common Harmful Algal Bloom-related disorders (HABs) include neurotoxic shellfish poisoning, ciguatera poisoning, paralytic shellfish poisoning, diarrhetic shellfish poisoning, and amnesic shellfish poisoning. Adapting to high temperatures and humidity, cyanobacteria also colonize historical sites, causing staining erosion, and reducing their aesthetic value. In this context, we have chosen carbonic anhydrase which plays an essential role in the interconversion of water and carbon dioxide to bicarbonates and makes it available to RuBisCo that regulates the photosynthetic pathways leading to cyanobacterial biomass generation. This study employed the molecular modeling approach to identify the potential natural inhibitors to carbonic anhydrase from the COCONUT database. Strategically we explore the Structural-Activity Relationship (SAR) of natural compounds to the reported sulphonamide inhibitors. Further, prediction-based online web servers such as pkCSM and SwissADME were used to determine the ADMET properties of the SAR molecules. An FDA-approved compound, Ethoxzolamide was chosen for comparative analysis. Next, the In-silico methodologies such as molecular docking and molecular dynamic simulations, free energy landscape analysis, hydrogen bond analysis, and binding free energy calculations were performed using various algorithms under virtual physiological conditions to identify potential SAR molecules against carbonic anhydrase. Further, we perform molecular dynamic simulation for a time period of 100 ns. It was evidenced from the molecular dynamic simulations and MM-PBSA calculations that some natural compounds outperform the Ethoxzolamide compound not only in stability but also in binding affinity. This study delves into the intricate interactions of natural compounds with the cyanobacteria carbonic anhydrase which plays a pivotal role in growth and development. Hence, we believe that our models could show extreme effectivity and might act as potent bio-algaecides.