Research

Understanding Protein Allostery 

We are very interested in understanding the function of biomolecules. Some of the interesting systems that we studied so far were: 1. Dimeric hemoglobin 2. HIV-1 reverse transcriptase 3. Green Fluorescent Protein 4 Photoactive Yellow Protein, etc., The main methodology, we have used is tracking the vibrational energy transport pathways. Two different methodologies have been used. In one method, considering the kinetic energy of the atoms, we start with a quenched structure and introduce an excitation in the form of a wave packet. From the propagation of the wave-packet, we could track the vibrational energy flow in the system. Alternatively, in another method, study the vibrational energy diffusivity using a heat current operator.  Both methodology details are provided in the reference below.

Reference:

Water Dynamics

    Water plays a vital role in protein allostery. So, it becomes inevitable to study the dynamics of water molecules embedded within the protein environment. The dynamics of water molecules depends upon the hydrophobic and hydrophilic nature of proteins, the availability of space, etc., The dynamics of water molecules in the confined region are of particular interest to us. For example, in the interfacial region of dimeric-HbI, in the GFP protein barrel, and in HIV-1 RT.  To better understand protein function, we also investigated the dynamics of hydrated water molecules on the surface of antifreeze protein. 

   In yet another interesting collaboration with THz spectrocopy work, we studied the dynamics of water molecules in the presence of alkali metal and halogen atoms existing in different concentrations. Here we explained the rattling motions (oscillations) of the anions and cations correlating with THz spectra.   Some of the references  are listed here:

 In silico Drug Design

Structure-based drug design was carried out for some interesting systems. Notable among them were 1. identifying a suitable drug for the carbonic anhydrase enzyme  and 2. bacterial adenylate cyclases.

Non- Covalent Interactions

In drug design, non-covalent interaction is important in identifying a suitable ligand. The contribution of non-covalent interaction energy cannot be neglected. Classical methods, although they identify the structural conformation, do not yield good results for non-covalent interaction energies due to hydrogen/halogen/pnicogen bonding, pi-pi interaction, pi-sigma bond interaction, etc. So, we need to depend on semi-empirical or quantum methods. Some of our interesting publications related to non-covalent interactions are listed here:

Normal Mode Analysis

The stability of a system can be determined by normal mode analysis (NMA). Most of the electronic structure packages use Cartesian coordinates for the vibrational spectra analysis. Transforming the cartesian coordinates to normal coordinates, i.e., in terms of bond length, bond angle, torsion, etc., we get a better picture of potential energy distribution. We carried out NMA on some interesting systems, which are listed below. But one drawback is that, NMA is mostly done within harmonic approximation. So, in the future, we are looking forward to understanding the anharmonic contribution to energy distribution.

Reaction Mechanism and conformational analysis

It is always interesting to study the reaction mechanism and conformational analysis for simple organic systems. Many collaborations in experimental research become great successes.  Some of the references are listed below.