Below are some other works going-on in the group and other collaborative works with experimental group.
1. Molecular dynamics studies to understand the role of thermostable direct hemolysin (TDH) intra-protomer disulphide in its oligomerization
We performed molecular dynamics of monomeric and dimeric forms TDH with and without disulphide bonds and observed that intra-protomer disulphide bond formed during folding or assembly of TDH restrains the C-terminal region. This restrained C-terminal region allows formation of inter-protomer contacts, thus facilitating TDH oligomerization (see image below).
Figure showing RMSF distribution of dimeric TDH. The c-terminal involved with interaction with other protomer does not show large RMSF.
2. Molecular dynamics studies to understand the role of Tyr 321 residue in oligomerization of Vibrio Cholrea Cytolysin (VCC)
The mutation of Tyr321Ala showed oligomerization and functional defective VCC protein. We performed extensive MD simulation of wild type and mutant protein to investigate the role of Y321 residue in oligomerization/function of VCC. We examined any possible long-range effect of the Y321A mutation on the monomeric structure of VCC. For this, we compared change(s) in the structural dynamics and network properties of the mutant, with respect to wild type VCC, using molecular dynamics (MD) simulations, and network analyses. We identified communities in both the wild type VCC and the Y321A using mutant correlation networks. As can be seen (see image below) the Y321A mutant shows drastic change in the dynamic sub-segments (communities) with fewer numbers of communities, and altered connectedness among them.
Figure showing differences observed in the Network communities in Wild type (left panel) and mutant (Y321A) in the right panel.
Both MD simulation and network analyses suggest that the residue-interactions involving the cradle loop, part of the pre-stem, 𝝱-Trefoil domain and 𝝱-Prism domain are affected in the Y321A mutant. Most likely, in Y321A mutant the hinge region of the pore-forming pre-stem motif imposes long-range defects within the VCC structure. Such defects, in turn, possibly affect the communications between different structural motifs/modules/domains surrounding the pore-forming pre-stem motif, thereby compromising their structural/conformational reorganization in the process of oligomeric pore-formation by the membrane-bound toxin monomers.
3. Prediction of curcumin binding site on VCC protein
We identified potential binding sites of curcumin on VCC protein using autodock tools and performed docking to show binding of curcumin on VCC (see image below).
Figure showing two potential binding of curcumin on VCC protein.
