Our Medicinal Chemistry Computational and Wet Lab focuses on the interdisciplinary field of drug design and synthesis, integrating computational methodologies and experimental approaches to advance pharmaceutical research. Our lab operates at the interface of chemistry, biology, and computational science, addressing critical challenges in drug discovery and development. By combining computational drug design techniques with cutting-edge synthetic methods, we aim to develop novel bioactive compounds with therapeutic potential against a range of diseases.
In the computational domain, we employ state-of-the-art tools for structure-based and ligand-based drug design. Using molecular dynamics (MD) simulations, we study the interactions between small molecules and target biomolecules, such as membrane proteins and enzymes, providing detailed insights into binding mechanisms and structure-activity relationships (SAR). Our lab specializes in free energy calculations using advanced methodologies, including MM-PBSA, FEP/MD, and TI/MD, to predict the binding affinities of ligands with high precision. Virtual screening of large chemical libraries enables us to identify potential lead compounds, leveraging both structure-based docking and ligand-based machine learning models. These computational approaches guide our synthetic efforts, narrowing down promising candidates for further experimental evaluation.
In our wet lab, we synthesize small molecules with specific biological activities, focusing on optimizing their pharmacological profiles. A significant area of our research is the design and synthesis of aminoadamantanes and related derivatives, which target influenza A M2 protein and its resistant strains (S31N, V27A, and others). These compounds are developed using a combination of rational design, informed by computational predictions, and innovative synthetic strategies. Our synthetic expertise also extends to creating novel antagonists and agonists for adenosine receptors, with the aim of discovering selective modulators for therapeutic applications. By integrating synthetic chemistry with computational predictions, we ensure a rational and efficient approach to drug discovery.
Another focus of our research is on neglected diseases, where we design and synthesize analogs of SQ109, an antitubercular compound, to inhibit the Mmpl3 bacterial transporter. These studies are complemented by collaborations with pharmacologists and biologists to evaluate the biological efficacy and safety of our compounds. Our collaborative network also includes researchers skilled in electrophysiology, ITC, and NMR spectroscopy, allowing us to comprehensively characterize drug-target interactions.
We also explore the conformational analysis of peptides and organic molecules using advanced NMR techniques, combined with MD simulations and quantum mechanical calculations. This work provides critical insights into the folding behavior of peptides and the role of non-conventional hydrogen bonds in molecular stability, which informs our design of peptide-based therapeutics.
Our lab is committed to bridging the gap between computational predictions and experimental validation, leveraging the synergy between computational tools and wet-lab techniques to streamline drug discovery. By focusing on structure-based drug design, SAR analysis, and synthetic chemistry, we aim to contribute to the development of innovative therapeutic agents. With a dedication to collaboration and innovation, the Medicinal Chemistry Computational and Wet Lab at NKUA is at the forefront of advancing medicinal chemistry and addressing unmet medical needs.
