Effects of Water Models on Binding Affinity: Evidence from All-Atom Simulation of Binding of Tamiflu to A-H5N1 NeuraminidaseReportar como inadecuado

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The Scientific World Journal - Volume 2014 2014, Article ID 536084, 14 pages -

Research Article

Institute for Computational Science and Technology, Quarter 6, Linh Trung Ward, Thu Duc District, Ho Chi Minh City, Vietnam

Institute of Physics, Polish Academy of Sciences, Aleja Lotnikow 32-46, 02-668 Warsaw, Poland

Received 31 August 2013; Accepted 5 November 2013; Published 2 February 2014

Academic Editors: R. Luo and K. Spiegel

Copyright © 2014 Trang Truc Nguyen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The influence of water models SPC, SPC-E, TIP3P, and TIP4P on ligand binding affinity is examined by calculating the binding free energy of oseltamivir carboxylate Tamiflu to the wild type of glycoprotein neuraminidase from the pandemic A-H5N1 virus. is estimated by the Molecular Mechanic-Poisson Boltzmann Surface Area method and all-atom simulations with different combinations of these aqueous models and four force fields AMBER99SB, CHARMM27, GROMOS96 43a1, and OPLS-AA-L. It is shown that there isno correlation between the binding free energy and the water density in the binding pocket in CHARMM. However, for three remaining force fields decays with increase of water density. SPC-E provides the lowest binding free energy for any force field, while the water effect is the most pronounced in CHARMM. In agreement with the popular GROMACS recommendation, the binding score obtained by combinations of AMBER-TIP3P, OPLS-TIP4P, and GROMOS-SPC is the most relevant to the experiments. For wild-type neuraminidase we have found that SPC is more suitable for CHARMM than TIP3P recommended by GROMACS for studying ligand binding. However, our study for three of its mutants reveals that TIP3P is presumably the best choice for CHARMM.

Autor: Trang Truc Nguyen, Man Hoang Viet, and Mai Suan Li

Fuente: https://www.hindawi.com/


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