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The three dimensional folded native structure of proteins is extremely important to conserve its
biological activity and to avoid unwanted immunological reactions. The native folded state of a
protein is so sensitive towards the nature of solvent under specific environmental conditions, that
with the change of solvent’s physicochemical properties the structure can be disrupted.1,2
Cosolvent like urea, guanidine, strong ionic detergents etc. are known to denature proteins whereas
the additives like some amino acids, polyhydric alcohols, sugars etc. generally stabilize the native
folded state of a protein. In spite of several studies, the underlying mechanisms of such events are
not clearly known. This made a scope for us to investigate the detailed protein-additive interactions
to explain cosolvent governed protein unfolding or stabilizing phenomenon. In the first part of my
presentation I shall discuss the behavior of a protein in various monohydric alcohol-water binary
mixtures at several alcohol concentrations under thermal stress.
3-6 This is essentially the case of
cosolvent governed unfolding of a protein. Further, I shall discuss about the concentration
dependent protecting role of amino acids as additive to preserve the structure of proteins.7
In all
such studies emphasis has been given to identify the interactions that play major role to initiate the
events. Attempts have been made to identify whether the cosolvents interact directly with the
protein or it follows an indirect mechanism to preserve or destruct protein’s folded forms.
In the second part of my presentation I shall discuss the parametrization of CHARMM polarizable
force filed for aldopentofuranoses and methyl-aldopentofuranosides based on the classical Drude
oscillator.
8 The work was done with the collaboration of CHARMM developer. We report a single
electrostatic model which is developed for eight different diastereoisomers of aldopentofuranoses
by optimizing the existing electrostatic and bonded parameters as transferred from ethers, alcohols,
and hexopyranoses to reproduce quantum mechanical (QM) dipole moments, furanose-water
interaction energies and conformational energies. Our developed model is found to reproduce both
QM data and experimental observables in an excellent manner. The final model obtained from this
study is transferrable for future studies on carbohydrates and can be used with the existing
CHARMM Drude polarizable force field for biomolecules.
References:
1. J. L. England, G. Haran, Annu. Rev. Phys. Chem. 2011, 62,257.
2. M. Q. Buck Rev. Biophys, 1998, 31,297.
3. D. Mohanta, M. Jana, J. Chem. Phys. 2016; 144,165101.
4. D. Mohanta, S. Santra, M. Jana, Phys. Chem. Chem. Phys. 2017, 19, 32636.
5. D. Mohanta, M Jana et al. J. Phys. Chem. A 2017, 121, 6172-6186
6. D. Mohanta, M. Jana Phys. Chem. Chem. Phys. 2018; 20,9886-9896.
7. S. Santra, M. Jana (submitted)
8. M. Jana, A. D. MacKerell Jr. J. Phys. Chem. B 2015, 119, 7846. |