Duangrudee Tanramluk, Ph.D., Asst. Prof.
My research experiences, ranging from quantum chemical calculations, protein X-ray crystallography, and software development, have shaped my vision and expertise on how to design tools to solve small molecule drug discovery problems. I choose scientific problems that have big impact on our scientific knowledge and the entire society. To fulfill this objective, I have identified 2 major protein groups, which are the kinases and DHFR. Kinases have been implicated in a lot of signaling pathways and human diseases, such as cancer and inflammation. DHFR can be the target protein for several antimicrobial drugs due to its high inhibitor selectivity nature.
The research goal is to be able to come up with algorithms that allow for binding affinity prediction to facilitate rational drug design from protein structure coordinates. A lot of drug researchers relies on combinatorial and high-throughput screening of chemical compounds instead of working towards chemical properties in a rational and interpretable way and leads to lead optimization failure. Based on trends of large amount of ligand interactomic distances, shape, and charge complementary in the homologous pockets from structure ensemble, we can now dissect the binding affinity in a human interpretable way for both aforementioned enzyme groups.
My key findings are around the Manoraa.org systems to assist drug discovery by linking ligand to target proteins, baseline expression, SNPs and pathways as featured in Nucleic Acids Research (webserver issue) (Tanramluk, et al. 2016). By linking these information in this Manoraa ligand design hub, researchers can perform in silico target discovery and ligand design before doing wet lab experiments. I have also developed Kinaree server to analyze features obtained from a set of homologous protein crystal structures which can guide inhibitor design. It enables us to compare the shape of the pocket, to observe position specific interactions, and to display chemical interactions in the pocket of the proteins (Tanramluk, 2009). My laboratory is equipped with glasses-free 3D laptop for biomolecular visualization supported by the Thailand Research Fund (Tanramluk, et al. 2013). Several visualization techniques are employed to create three-dimensional pictures from various perspectives. The effects from parameters therein, such as the entities that usually participate in hydrogen bond formation, the parts of the pocket that expand or contract upon binding to inhibitors, can be displayed to guide scientists while formulating an inhibitor design strategy.
Taken together, I gear toward novel computational methods to make drug discovery faster, cheaper, and more effective.
1. *Tanramluk D, Narupiyakul L, Akavipat R, Gong S, Charoensawan V. MANORAA (Mapping Analogous Nuclei Onto Residue And Affinity) for identifying protein-ligand fragment interaction, pathways and SNPs. Nucl. Acids Res 2016, 44 (W1): W514-W521.