• Date: 07/19/2017 06:11 PM
  • Location S. N. Bose National Centre for Basic Sciences (Map)

Description

ABSTRACT

The present thesis documents detail investigations of the protein structure, conformation, hydration and enzyme activity in presence of different kinds of cosolutes (e.g. macromolecules, osmolytes, chemical denaturants) at the physiological condition. Our goal is to understand how the protein folds/unfolds, hydrates and function in the cellular crowded environment* by in vitro study. With an eye to this, we have chosen some synthetic polymers and some bio-relevant small cosolutes to study protein stability by both spectroscopy and thermodynamic studies. We have found some interesting physical properties of the protein which is indeed correlated to the real cellular phenomena. We have revealed the effect of short chain polyethylene glycol (PEG) on the physical properties of a model protein human serum albumin (HSA) and find an unusual behavior in thermal stability as well as in the hydration of the protein which cannot be explained only by the so called *excluded volume theory, rather it is related to some weak attractive interactions between protein and PEG. We have addressed a debatable issue whether the protein denatures (or stabilizes) due to modification of water network by using some well-known denaturing agents (Urea, GdmCl) and osmolytes (amino acids). Our finding using terahertz (THz) spectroscopy tool reveals the interesting correlation of protein stabilization or denaturation with the modification in collective hydrogen bond dynamics of water in sub-ps to ps time scale. Finally, we have studied enzyme activity in presence of cosolutes and found an unusual enhancement of activity in very dilute concentration region of cosolutes whereas activity decreases in the higher concentration regime. The basic results presented here bare implications for the study of protein stability and activity in real biological environments.


List of publications related to the thesis:

1.         Samanta, N., Mahanta, D. D., Hazra, S., Kumar, G. S., and Mitra, R. K. (2014) Short Chain Polyethylene Glycols Unusually Assist Thermal Unfolding of Human Serum Albumin, Biochimie 104, 81-89.


2.         Samanta, N., Mahanta, D. D., and Mitra, R. K. (2014) Does Urea Alter the Collective Hydrogen Bond Dynamics in Water: A Dielectric Relaxation Study in the THz Frequency Region, Chemistry - An Asian Journal 9, 3457-3463.


3.         Samanta, N., Mahanta, D. D., and Mitra, R. K. (2014) Collective Hydration Dynamics of Guanidinium Chloride Solutions and its Possible Role in Protein Denaturation: A Terahertz Spectroscopic Study, Physical Chemistry Chemical Physics 16, 23308-23315.


4.         Samanta, N., Mahanta, D. D., and Mitra, R. K. (2015) Urea and guanidinium chloride act as ‘water structure breakers’: The debate revisited by dielectric relaxation study in THz range, Infrared, Millimeter, and Terahertz waves (IRMMW-THz), 2015 40th International

Conference, IEEE.(Conference Proceeding)


5.         Samanta, N., Luong, T. Q., Mahanta, D. D., Mitra, R. K., and Havenith, M. (2016) Effect of Short Chain Polyethyleneglycols on the Hydration Structure and Dynamics around Human Serum Albumin,

Langmuir.32(3), 831-837.


6.         Samanta, N., Mahanta, D. D., Choudhury, S., Barman, A., and Mitra, R. K. (2017) Collective Hydration dynamics in some amino acid solutions: A combined GHz-THz Spectroscopy study, Journal of Chemical Physics 146 (12),  25101-125108.


7.         Samanta, N., Mahanta, D. D., and Mitra, R. K. THz spectroscopic study unravels why chloride salt of guanidinium is a protein denaturing agent while sulphate salt is not (Manuscript to be submitted).


8.         Samanta, N., Mahanta, D. D., Patra, A., and Mitra, R. K. Lysozyme activity on Micrococcus Lysodeikticus cell wall in crowded environments (Manuscript to be submitted).


Other publications:

9.         Mahanta, D. D., Samanta, N., and Mitra, R. K. (2016) The effect of  monovalent cations on the collective dynamics of water and on a model protein, Journal of Molecular Liquids 215, 197-203.


10.       Patra, A., Hazra, S., Samanta, N., Kumar, G. S., and Mitra, R. K. (2016) Micelle induced dissociation of DNA–ligand complexes: The effect of ligand binding specificity, International journal of biological macromolecules 82, 418-424.


11.       Mahanta, D. D., Patra, A., Samanta, N., Luong, T. Q., Mukherjee, B., and Mitra, R. K. (2016) Non-monotonic dynamics of water in its binary mixture with 1,2-dimethoxyethane: A combined THz spectroscopic and MD simulation study, The Journal of Chemical Physics 145, 164501-164512.


12.       Patra, A., Samanta, N., Das, D. K., and Mitra, R. K. Enhanced catalytic activity of α-chymotrypsin in cationic surfactant solutions: The component specificity revisited Journal of Physical Chemistry B 121, 1457-1465.


13.       Mahanta, D. D., Samanta, N., and Mitra, R. K. The Decisive Role of Hydrophobicity on the Effect of Alkylammonium Chlorides on Protein Stability: A Terahertz Spectroscopic Finding (on revision).


14.       Pal, S., Samanta, N., Mahanta, D. D., Mitra, R. K., and Chattopadhyay A. Effect of phospholipid head group on the structure and dynamics of water around membrane bilayers: A THz study (Manuscript to be submitted).


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