Over the last few decades, computer-aided drug design has emerged as a powerful technique playing a crucial role in the development of new drug molecules. Structure-based drug design and ligand-based drug design are two methods commonly used in computer-aided drug design. In this article, we discuss the theory behind both methods, as well as their successful applications and limitations. To accomplish this, we reviewed structure based and ligand based virtual screening processes. Molecular dynamics simulation, which has become one of the most influential tool for prediction of the conformation of small molecules and changes in their conformation within the biological target, has also been taken into account. Finally, we discuss the principles and concepts of molecular docking, pharmacophores and other methods used in computer-aided drug design.
Caspase-3 has been identified as a key mediator of neuronal apoptosis. The present study identifies caspase-3 as a common player involved in the regulation of multineurodegenerative disorders, namely, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). The protein interaction network prepared using STRING database provides a strong evidence of caspase-3 interactions with the metabolic cascade of the said multineurodegenerative disorders, thus characterizing it as a potential therapeutic target for multiple neurodegenerative disorders. In silico molecular docking of selected nonpeptidyl natural compounds against caspase-3 exposed potent leads against this common therapeutic target. Rosmarinic acid and curcumin proved to be the most promising ligands (leads) mimicking the inhibitory action of peptidyl inhibitors with the highest Gold fitness scores 57.38 and 53.51, respectively. These results were in close agreement with the fitness score predicted using X-score, a consensus based scoring function to calculate the binding affinity. Nonpeptidyl inhibitors of caspase-3 identified in the present study expeditiously mimic the inhibitory action of the previously identified peptidyl inhibitors. Since, nonpeptidyl inhibitors are preferred drug candidates, hence, discovery of natural compounds as nonpeptidyl inhibitors is a significant transition towards feasible drug development for neurodegenerative disorders.
Natural products from the unique environments of sea water and oceans represent a largely unfamiliar source for isolation of new microbes, which are potent producers of secondary bioactive metabolites. These unique life-forms from the marine ecosphere have served as an important source of drugs since ancient times and still offer a valuable resource for novel findings by providing remedial treatments. Therefore, it can be expected that many naturally bioactive marine microbial compounds with novel structures and bioactivities against those from terrestrial environments may be found among marine metabolites. Biofilms in aquatic environment possess serious problems to naval forces and oceanic industries around the globe. Current anti-biofilm or anti-biofouling technology is based on the use of toxic substances that can be harmful to their surrounding natural locales. Comprehensive research has been done to examine the bioactive potential of marine microbes. Results are remarkably varied and dynamic, but there is an urgent need for bioactive compounds with environmentally friendly or “green” chemical activities. Marine microbes have the potential as upcoming and promising source of non-toxic compounds with sustainable anti-biofouling/anti-biofilm properties as they can produce substances that can inhibit not only the chemical components required for biofilm production but also the attachment, microorganism growth, and/or cell–cell communication.
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