Project 1

Understanding the structural differences between ApoE3 and ApoE4

Alzheimer’s disease (AD) is a common neurodegenerative disease characterized by the formation of neurofibrillary tangles and plaques in the brain, leading to neuronal dysfunction, neuronal loss and finally death . The increased risk of developing AD is associated with the ApoE gene, which encodes the variants, ApoE2, ApoE3 and ApoE4. ApoE4 is known to be the strongest causative factor for late-onset AD and contains the mutation C112R. The relationship between the structure of ApoE isoforms and their contribution to the cause of AD is still not known completely.

My primary goal was to explore structural differences between ApoE3 and ApoE4 by all-atom MD simulations, Umbrella Sampling and Markov State Modeling techniques. The preliminary free energy calculations indicated that ApoE4 is energetically less stable as compared to ApoE3 by 1.76kcal/mol which corroborates with experimental findings. I have also seen some strong structural differences between the two isoforms on the basis of their secondary structures, contact-map, salt-bridges involved and domain-domain interactions. I could also successfully locate the regions of ApoE4 isoform that are affected the most due to a single change of Cysteine/Arginine at position 112.

Project 2

Structure and Dynamics Simulation of RNA bulges and pseudo-continuous helices

Prof. Bhattacharyya’s group analyzed all available RNA structures and found quite a few fragments of double helices containing bulges and pseudo-continuous helices. I extended the project towards understanding the role of such discontinuity (bulges or pseudohelices) in terms of stability and flexibility. The major outcomes of this project was that one could specifically see the effect of bulge-type on the RNA double helix. My key individual achievement in this project was to report the various parameters (based on both charmm36 and AMBER99SB force fields) related to base pairing at the junction of a bulge containing RNA or at the junction of a pseudohelix. Such systematic catalog of data related to bugles or pseudohelices was lacking in literature.

Project 3

A comparative overview of four different human telomeric quadruplex topologies by applying various Computational techniques.

My main success in this study was (a) to report the structural properties (previously unavailable in literature) of G-quadruplexes in terms of base pair parameters, stacking geometry and backbone conformations as obtained by charmm-27 force field, (b) to predict (based on bothe MD and SMD studies) that the most 3D structure adopted by telomeres is the anti-parallel topology, although the mixed-(3 + 1)-form1 should not be completely neglected while considering major conformation, and (c) to conclude that all G-rich sequences may not adopt a topology similar to the ones adopted by G-rich sequences of the telomeric region. The results of this project were published in Ray et. al., Biopolymers, 2015, 105(2), pp 83-99

Project 4

Insights into oxidative tearing of nano-size Graphene sheets by Quantum Chemical Approach along with validation by experiment.

My main aim of this project was to investigate this procedure by ab initio density functional theory method. My key achievement in this project was that I could state: (a) the tearing of a graphene sheet always starts from a cis-edge, breaking H-C-(C-C)-C-H bonds, and (b) progressive tearing of a large graphene sheet into smaller ones would lead to smaller graphene sheets with an increase in the percentage of trans-edge, i.e., −(C–C–C)– bonding predominant at the edges with some functionalization at the terminal C-atoms. This project involved experimental collaborators who performed experiments of magnetic hysteresis. The experimental results complemented my theoretical findings. This work was published in Ray et. al., J. Phys. Chem. C, 2015, 119(2), pp 951-959.

Project 5

Characterization of Unfolding Mechanism of Human Lamin A ig Fold.

This work was carried out as a part of a bigger experimental project that looked into the implications of unfolding of human lamin A Ig fold (caused due to mutation R453W) in Emery–Dreifuss Muscular Dystrophy. It was published in Bera et al., Biochemistry, 2014, 35:7247-7258. The computation section was solely performed by me. I could predict how a stretching mechanical perturbation destabilizes the mutant R453W, and compared the mechanoelastic properties of the mutant with that of the wild-type in conjunction with SMD.

Project 6

Role of structure and environment on excited state H-bonding Fluorescent Probe

Prof. Bhattacharyya's experimental collaborators synthesized and characterized an environment sensitive fluorescent probe, 11-benzoyl-dibenzo[a,c]phenazine (BDBPZ), that acts via excited state hydrogen bonding (ESHB). This newly synthesized derivative BDBPZ is much more interactive as compared to its parent molecule dibenzo[a,c]phenazine (DBPZ), due to the benzoyl group that is flanked outside the skeletal aromatic rings of DBPZ, which helps to sense the environment properly and thus shows better ESHB capacity than DBPZ. I have performed the computational section and predicted the non-planarity in the structure of the molecule in excited state (ES) along with predicting the H-bonding pattern in ES. This work was published in Dey et al., J. Luminiscence, 2016, 173:105-112.