Drug Discovery and Design
Drug discovery and design is the process of identifying new medications or therapeutics and optimizing them for use as pharmaceutical treatments. It involves several stages and disciplines, integrating aspects of biology, chemistry, pharmacology, and computational modeling.
Drug discovery and design has profound applications in understanding disease mechanisms, developing new treatments, personalizing medicine, and advancing pharmaceutical innovation. Through these efforts, researchers and pharmaceutical companies aim to improve health outcomes and address a wide range of medical conditions.
Virtual Screening of Natural Product Compounds Targeting Mutant Forms of p53 Protein for Cancer Therapeutics
Lung cancer is the leading cause of cancer-related deaths in men worldwide, while breast cancer leads to the highest number of cancer deaths in women. Understanding the molecular biology of these cancers is crucial, particularly by identifying and analyzing the mutations driving their progression.
Given that somatic mutations occur more frequently than germline mutations, they present significant opportunities for research. Among these, the TP53 gene is one of the top three genes harboring somatic mutations linked to both lung and breast cancers.
TP53 encodes the tumor protein p53, a 393-amino-acid protein essential in preventing cancer development. Mutations in p53 are not only prominent in lung and breast cancers but are also found in more than 50% of all human cancers.
This research focuses on conducting virtual screening of several key p53 mutants (namely, E285K, G245C, R158L, R175H, R175L, R248L, R248Q, R248W, R249S, R273C, R273H, R273L, V157F, Y163C, and Y220C) associated with lung and breast cancers. The structures of these mutants, obtained from Molecular Dynamics Simulations, will be screened against natural product database (60,921 compounds), opening new avenues for potential therapeutic interventions.
Targeting Aldehyde Dehydrogenase: A Virtual Screening Approach Using Natural Product Databases
Aldehyde dehydrogenases (ALDHs) are a family of enzymes that catalyze the oxidation of aldehydes to carboxylic acids, playing a vital role in detoxification and metabolism. Found in various tissues, ALDHs help process toxic byproducts, including those from alcohol metabolism. Alterations in specific ALDH isoforms are linked to diseases such as cancer, neurodegenerative disorders, and metabolic syndromes.
Inhibiting ALDH proteins offers significant therapeutic benefits, particularly in cancer and neuroprotection. Some ALDH isoforms are linked to cancer stem cells, contributing to tumor growth and treatment resistance. Targeting these enzymes can enhance cancer therapy efficacy. Additionally, inhibiting specific ALDHs may reduce oxidative stress, making it a potential strategy for neurodegenerative diseases. Overall, ALDH inhibition can provide insights into metabolic pathways and address conditions involving aldehyde accumulation.
Our research group is conducting a virtual screening study using natural product database of 60,921 compounds to identify potential ALDH inhibitors. Utilizing AutoDock Vina, we will simulate docking interactions between these natural compounds and various ALDH isoforms to predict binding affinities. This in silico approach aims to discover novel inhibitors for therapeutic applications in cancer treatment and other ALDH-related conditions, leveraging the diversity of natural products.
Molecular Docking of Urease Inhibitors: A Step Towards New Treatments for Gastric Ulcers
Urease is a metalloenzyme that catalyzes the hydrolysis of urea into ammonia and carbon dioxide, playing a vital role in nitrogen metabolism. Produced by pathogenic bacteria like Helicobacter pylori, urease raises local pH levels, facilitating bacterial survival in the acidic stomach. Understanding its structure and function is crucial for developing targeted inhibitors to combat its pathogenic effects.
Inhibiting urease offers significant therapeutic benefits, particularly for gastrointestinal health. Reduced urease activity lowers ammonia production, decreasing local pH and enhancing the efficacy of antibiotics against Helicobacter pylori. This leads to less gastric inflammation and ulcer formation. Additionally, urease inhibitors can improve nitrogen use in agriculture, reducing environmental impact. Thus, effective urease inhibitors are promising for both medical and agricultural applications.
Our research group is conducting a study using AutoDock Vina to identify potential inhibitors from a local library of compounds. This in silico approach predicts binding affinities and interactions between compounds and urease, guiding the development of novel therapeutics aimed at improving treatment outcomes for gastric ulcers and related disorders.