ASM 2019

Talk (C17)


Microscopic investigations of a model peptide in presence of alcohol and their relevance for cholecystokinin-8: A molecular dynamics simulation study

 

Apramita Chand1, Pragin Chettiyankandy2, Snehasis Chowdhuri2

1National Institute for Science Education and Research, Bhubaneswar

2Indian Institute of Technology, Bhubaneswar

Abstract

We have carried out classical molecular dynamics simulations to explore the aqueous solvation structure, dynamics and hydrogen bond properties of a model peptide, N- methylacetamide(NMA) in presence of two alcohols: ethanol(EtOH) and 2,2,2 trifluoroethanol(TFE). From radial distribution functions, average hydrogen bond number and energy, we have observed that ethanol facilitates hydration of NMA molecules whereas TFE sustains inter-amide hydrogen bonds. It is seen that together, NMA and TFE molecules separate out regions of water molecules whereas this clustering effect is not as visible in EtOH solution1. The relevance of some of these observations have been tested in case of cholecystokinin- 8(CCK-8), a peptide which has been known to modify alcohol-induced behavioural patterns and whose receptor binding properties have been known to be affected in presence of alcohol2-5. Hydrogen bonding interactions between terminal residues like phenylalanine and asparagine and water are most prominent in aqueous ethanol solutions while in presence of TFE, these residues prefer to interact with the alcohol than with water, a trend which has been noted in case of NMA earlier. Additionally, in both cases (that of the model peptide as well as in CCK-8), solvation of hydrophobic groups is reduced with addition of alcohol, that is more apparent in TFE solutions. Finally, the conformational characteristics of CCK-8, tested through clustering analysis and changes in helical tendencies, have been proposed to be affected by the aqueous alcohol solution properties6, which show striking similarities in simulations involving both the model peptide, NMA, as well as cholecystokinin-8.

References

 

1.      Chand, A.; Chowdhuri, S. J. Mol. Liq. 2016, 224, 1370-1379.

2.      Evangelista, S.; Maggi, C. Br. J. Pharmacol. 1991, 102 (1), 119-122.

3.      Pandol, S. J.; Periskic, S.; Gukovsky, I.; Zaninovic, V.; Jung, Y.; Zong, Y.; Solomon, T. E.; Gukovskaya, A. S.; Tsukamoto, H. Gastroenterology 1999, 117 (3), 706-716.

4.      Toth, P.; Shaw, C.; Perlanski, E.; Grupp, L. Pharmacol. Biochem. Behav. 1990, 35 (2), 493-495.

5.      Harro, J.; Wahlström, G.; Oreland, L. Alcohol Alcohol 1994, 29 (5), 575-581.

6.      Chand, A.; Chettiyankandy, P.; Chowdhuri, S. In Soft Computing for Problem Solving; Springer, 2019; pp 25-40.

 

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