Molecular Dynamics Simulation

Aminoacyl-tRNA synthetases are an indispensable component of ribosomal protein translational machinery and have been validated as potential drug target for malaria. The dynamic conformational landscape of Plasmodium tyrosyl-tRNA synthetase has been analysed in the presence and absence of bound ligand. All-atom simulations with cumulative time scale of microseconds show quantitative differences in the conformational diversity of this enzyme.

Datt M*

Interplay of substrate polymorphism and conformational plasticity of Plasmodium tyrosyl-tRNA synthetase.

Computational Biology and Chemistry, Vol. 95, Dec 2021.

Molecular Docking

We have explored the prospects of repositioning the repertoire of approved drugs and natural products for potentially inhibiting malarial protein translation machinery. Molecular docking of a diverse set of small molecules with lysyl-, prolyl-, and tyrosyl- synthetases from Plasmodium and humans helped us identify promising lead molecules. Overall, this study provides an exciting foundation for the development of specific antimalarials.

Doshi K, Pandya N, Datt M*.

In silico assessment of natural products and approved drugs as potential inhibitory scaffolds targeting aminoacyl-tRNA synthetases from Plasmodium.

3 Biotech. 2020 Nov;10(11):470. doi: 10.1007/s13205-020-02460-6. Epub 2020 Oct 12. PMID: 33088666; PMCID: PMC7550503.

Computational Structural Biology

Understanding protein structure is indispensable to decipher molecular underpinning of physiological functions. Protein structure is a collection of Cartesian coordinates of atoms within the covalently connected amino-acids. I use computational methods to study 3D structures of proteins. Iterative calculation of convex hull layers in the structures have provided interesting insights in to the packing of atoms in the proteins. The figure below shows coordinates of C-alpha atoms of a proteins structure (left) and right image shows same set of coordinates colored according to different convex hull layers.

Reference: Geometric analysis of the conformational features of protein structures (BIOMAT 2015)

Computational Structural Chemistry

Natural Products (NPs) are chemical compounds that exist within the living systems. These molecules are suitable candidates for lead discovery. Molecular descriptor based evaluation of chemical space for NPs has provided interesting insights into their drug-likeliness. A details comparison of NPs from two different databases and FDA approved drugs highlights the potential for NPs as lead molecules. The figure below show the distribution of molecules based on quantitative estimation of drug-likeness (QED) in two NPs databases and their comparison with approved drugs.