Correlation between protein bond vector & dihedral fluctuation:

Dihedral fluctuations are not directly amenable due to the limitation of the experimental probe. NMR experiments probe dipolar fluctuations given in terms of cross-correlated relaxation (CCR) rates, given by the zero frequency spectral density function of the fluctuations. Here, we calculate the zero frequency spectral function from molecular dynamics trajectories for dipolar and dihedral angle fluctuations and show that they are correlated. Thus, the CCR can be a marker of dihedral fluctuations.

Conformational fluctuations in the molten globule state of α-lactalbumin

A molten globule (MG) state is an intermediate state of a protein observed during the unfolding of the native structure. We consider a milk protein, α-lactalbumin (aLA), which shows an MG state at low pH upon removal of the calcium (Ca2+) ion. We use the dihedral principal component analysis, the density based clustering method, and the machine learning technique to identify the conformational fluctuations of protein at MG state. 

The functionality of proteins at the molten globule state

In this project, we characterize binding of aLA with OA microscopically.  We find the binding mode between MG-aLA and OLA using the conformational thermodynamics method. We also estimate the binding free energy using the umbrella sampling (US) method for both the MG state and the neutral state. Furthermore, we find that the binding free energy obtained from the US is comparable with earlier experimental results.

Water dynamics at the interface

Water molecules present at the surface of protein (Interfacial water, IW) play an important role in mediating protein ligand interactions. We probe the dynamics of interfacial water in BAMLET complex.  We find water molecules that are close to both protein and ligand have slower residence time and mean square displacement, suggesting the heterogeneous behavior of water at the protein-ligand interface. 

Coarse-grained model of the protein

Sometimes one needs a coarse grained (CG) model to describe complex cellular phenomena. We build a CG model of proteins with structural information based on an effective force field obtained from all-atom molecular dynamics simulations. Each bead is assigned a couple of degrees of freedom, representing the backbone dihedral angles.  We show that using such a model, one can reproduce the protein structure comparable to the crystal structure well. This can pave the way for CG models with structural information.