Studies of Molecular Energy Changes in AQP5 in the Presence and Absence of Water Using Computational Method

Ahmad Alaei, Mehdi Pooladi, Soheila Karani, Saba Abolhasan Dust



Aquaporins (AQPs) are water channel proteins. Up to now, 13 AQPs have been known in mammals. AQPs play a key role in water osmotic flow in various cells. the members of aquaporin protein family have been identified as H2O transposters across organelle and plasma membranes. AQPs of the aquaammoniaporin type are highly permeable for water and ammonia. In this study, we have evaluated the structure of AQP5 using two computational methods. We investigated the potential and kinetic energy, as well as maximum and minimum difference of atomic charge for AQP5. The atomic study of AQP5 protein showed that the minimum and maximum value of atomic charge in the presence and absence of water were related to sections (1-15). The water effect is generally considered to be the major driving force in the folding of AQP5. different sections of AQP5 behaved different in the presence or absence of water, and have different functionalities. Also, the absolute value of atomic charge difference for AQP5 sections was proven as an important feature in protein structural changes.

•AQP5’s function and structure are dependent on the presence and absence of water.
•The presence of water molecules around AQP5 protein causes changes in dynamic properties.
•The optimum functions of AQP5 are arisen at low energy levels and the presence of water.
•kinetic energy for AQP5 protein in mode of no water has the lowest fluctuations but in presence of water considerable fluctuations are seen.


Aquaporins; Computational simulation; Energy; Membrane Channel; Water.

Full Text:



Borgnia, M., Nielsen, S., Engel, A., and P. Agre, (1999). "Cellular and molecular biology of the aquaporin water channels." Annu. Rev. Biochem., 68: 425–458.

Cho, G., Bragiel, A. M., Wang, D., Pieczonka, T. D., Mariusz, T., Skowronski, C., Shono, M., Nielsen, S., and Y. Ishikawa, (2015). "Activation of muscarinic receptors in rat parotid acinar cells induces AQP5 trafficking to nuclei and apical plasma membrane." Biochim. Biophys. Acta, 1850 (4): 784-793.

De Groot, B. L., and H. Grubmüller, (2005). "The dynamics and energetics of water permeation and proton exclusion in aquaporins." Curr. Opin. Struct. Biol., 15(2): 176-183.

Direito, I., Madeira., A., Brito, M. A., and G. Soveral, (2016). "Aquaporin-5: from structure to function and dysfunction in cancer." Cell Mol. Life Sci., 73 (8): 1623-1640.

Hashido, M., Kidera, A., and M. Ikeguchi, (2007). "Water transport in Aquaporins: Osmotic Permeability Matrix Analysis of Molecular Dynamics Simulations." Biophys. J., 93 (2): 373-385.

Horsefield, R., Nordén, K., Fellert, M., Backmark, A., Törnroth-Horsefield, S., Terwisscha Van Scheltinga, A.C., Kvassman, J., Kjellbom, P., Johanson., U., and R. Neutze, (2008). "High-resolution x-ray structure of human aquaporin 5." Proc. Natl. Acad. Sci. USA, 105 (36): 13327-13332.

Huang, Z., Chen, F., Yu, C., and X. Gao, (2010). "Expression and the correlation of AQP5, HIF-1alpha and VEGF in human nasal polyps." J. clinic. Otorhinolaryng., head, and neck surg., 24(10): 458-461.

Hub, J.S., Grubmüller, H., and B. L. De-Groot (2009). "Dynamics and energetics of permeation through aquaporins.What do we learn from molecular dynamics simulations?." Handb. Exp. Pharmacol., 190: 57-76.

Jackson, M. B., (2006). "Molecular and Cellular Biophysics." Cambridge University Press, New York.

Janosi, L., and M. Ceccarelli, (2013). "The gating mechanism of the human aquaporin 5 revealed by molecular dynamics simulations." PLoS One, 8 (4): e59897.

Ishikawa, Y., Yuan, Z., Inoue, N., Skowronski, M.T., Nakae, Y., Shono, M., Cho, G., Yasui, M., Agre, P., and S. Nielsen, (2005). "Identification of AQP5 in lipid rafts and its translocation to apical membranes by activation of M3 mAChRs in interlobular ducts of rat parotid gland." Am. J. Physiol. Cell Physiol., 289 (5): 1303-1311.

Kedem, O., and A. Katchalsky, (1989). "Thermodynamic analysis of the permeability of biological membranes to non-electrolytes." Biochim. Biophys. Acta, 1000: 413-30.

Khaghani-Razi-Abad, S., Hashemi, M., Pooladi, M., Entezari, M., and E. Kazemi, (2015). "Proteomics analysis of human oligodendroglioma proteome." Gene, 569 (1): 77-82.

Lee, H. J., Jee, B. C., Kim, S. K., Kim, H., Lee, J. R., Suh, C. S., and S. H. Kim, (2016). "Expressions of aquaporin family in human luteinized granulosa cells and their correlations with IVF outcomes." Hum. Reprod., 31(4): 822-831.

Martínez-Ballesta-Mdel, C., and M. Carvajal, (2016). "Mutual Interactions between Aquaporins and Membrane Components." Front Plant Sci., 7: 1322.

Mobasheri, A., and R. Barrett-Jolley, (2014). "Aquaporin Water Channels in the Mammary Gland: From Physiology to Pathophysiology and Neoplasia." J. Mammary Gland Biol. Neoplasia, 19 (1): 91-102

Parisi, M., C. and C. Ibarra, (1996). "Aquaporins and water transfer across epithelial barriers." Braz. J. Med. Biol. Res., 29 (8): 933-939.

Pooladi, M., Khaghani-Razi-Abad, S., and M. Hashemi, (2014). "Proteomics analysis of human brain glial cell proteome by 2D gel." Indian J. Cancer, 51 (2): 159-162.

Schönfelder, J., De Sancho, D., and R. Perez-Jimenez, (2016). "The Power of Force: Insights into the Protein Folding Process Using Single-Molecule Force Spectroscopy." J. Mol. Biol., 428 (21): 4245-4257.

Shahmansoorian, E., Hashemy, M., Ahmadi, S., Jamali, Z., Asghari Moghaddam, N., and R. Rasoolzadeh, (2014). " Theoretical Studies of AQP4 in Water & Gas Phases Nano Simulation of the Monte Carlo Method by Molecular Mechanics Force Fields." Orient. J. Chem., 30(3):1303-1310

Sherrill, CD, (2000). " An Introduction to Hartree-Fock Molecular Orbital Theory." School of Chemistry and Biochemistry Georgia Institute of Technology, [Online].

Stansfeld, P.J., and M. S. P. Sansom, (2011). "Molecular simulation approaches to membrane proteins." Structure, 19 (11): 1562–1572.

Sui, H., Han, B.G., Lee, J.K., Walian., P., and B.K. Jap, (2001). "Structural basis of water specific transport through the aqp1 water channel." Nature, 414 (6866): 872–878.

Tohidi, S., Monajjemi, M., and A. Rustaiyan, (2015). "Monte Carlo Study of Aquaporin, 1, 4 and 5 as the Nano Channel Membrane." J. Comput. Theor. Nanoscience, 12(11):4345–4351.

Wang, Y., and E. Tajkhorshid, (2007). "Molecular mechanisms of conduction and selectivity in aquaporin water channels." J. Nutr., 137 (6 Suppl 1): 1509S-1515S.

Yu, L., Rodriguez, R. A., Chen, L. L., Chen, L. Y., Perry, G., Mchardy, S. F., and C. K. Yeh, (2016). "1,3-propanediol binds deep inside the channel to inhibit water permeation through aquaporins." Protein Sci., 25 (2): 433-441.

Yubao, C., and D. A. Bastien, (2011). "Water transport in human aquaporin-4: Molecular dynamics (MD) simulations." Biochem. Biophys. Res. Commun., 412 (4): 654-659.

Zhang, Y.B. and L. Y. Chen, (2013). "In silico study of Aquaporin V: Effects and affinity of the central pore-occluding lipid." Biophys. Chem., 171, 24-30.

Zeuthen. T., (2000). "Molecular water pumps." Rev. Physiol. Biochem. Pharmacol., 141: 97-151.

Zeuthen, T. and D. A. Klaerke, (1999). "Transport of water and glycerol in aquaporin 3 is gated by H (+)." J. Biol. Chem., 274 (31): 21631-21636.


  • There are currently no refbacks.