Nanobiological studies on drug design using molecular mechanic method

Authors
Hooria Seyedhosseini Ghaheh 1
Maryam Mousavi 2
Mahmood Araghi 3
Reza Rasoolzadeh 1
Zahra Hosseini 4
1 Young Researchers and Elites Club, Science and Research Branch, Islamic Azad University, Tehran, Iran
2 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
3 Department of Pathology, Amir-Momenin Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
4 Department of Public Health, Isfahan University of Medical Sciences, Isfahan, Iran
Abstract
Background: Influenza H1N1 is very important worldwide and point mutations that occur in the virus gene are a threat for the World Health Organization (WHO) and druggists, since they could make this virus resistant to the existing antibiotics. Influenza epidemics cause severe respiratory illness in 30 to 50 million people and kill 250,000 to 500,000 people worldwide every year. Nowadays, drug design is not done through trial and error because of its cost and waste of time; therefore bioinformatics studies is essential for designing drugs.
Materials and Methods: This paper, infolds a study on binding site of Neuraminidase (NA) enzyme, (that is very important in drug design) in 310K temperature and different dielectrics, for the best drug design. Information of NA enzyme was extracted from Protein Data Bank (PDB) and National Center for Biotechnology Information (NCBI) websites. The new sequences of N1 were downloaded from the NCBI influenza virus sequence database. Drug binding sites were assimilated and homologized modeling using Argus lab 4.0, HyperChem 6.0 and Chem. D3 softwares. Their stability was assessed in different dielectrics and temperatures.
Result: Measurements of potential energy (Kcal/mol) of binding sites of NA in different dielectrics and 310K temperature revealed that at time step size = 0 pSec drug binding sites have maximum energy level and at time step size = 100 pSec have maximum stability and minimum energy.
Conclusions: Drug binding sites are more dependent on dielectric constants rather than on temperature and the optimum dielectric constant is 39/78.

Keywords

1.
Chen CY, Huang HJ, Tsai FJ. Drug design for Influenza A virus subtype H1N1. J Taiwan Ins Chem Eng 2010;41:8-15.  Back to cited text no. 1
    
2.
Anh Nguyen TN, Dao TT, Tung BT, Choi H, Kim E. Influenza A (H1N1) neuraminidase inhibitors from Vitis amurensis. Food Chem 2011;124:437-43.  Back to cited text no. 2
    
3.
Wang B, Dwyer DE, Blyth CC, Soedjono M, Shi H, Kesson A, et al. Detection of the rapid emergence of the H275Y mutation associated with oseltamivir resistance in severe pandemic influenza virus A/H1N1 09 infections. Antiviral Res 2010;87:16-21.  Back to cited text no. 3
    
4.
Noorifard M, Khoshdel AR, Hosseini Shokouh SJ. A review in novel pandemic H1N1 A. J Army Univ Med Sci Iran 2009;3:228-40.  Back to cited text no. 4
    
5.
Treanor JJ. Influenza viruses including avian influenza and swine influenza. In: Mandell GL, Bennett GE, Dolin R, editors. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 7 th ed. Philadelphia: Churchill Livingstone; 2009. p. 2265-88.  Back to cited text no. 5
    
6.
Qi-Shi Dua bd, Wang SQ, Huang RB, Chou KC. Computational 3D structures of drug-targeting proteins in the 2009-H1N1 influenza A virus Chemical Physics. Letters 2010;482:191-5.  Back to cited text no. 6
    
7.
Arias CF, Escalera-Zamudio M, Soto-Del Rio ML, Cobian-Guemes AG, Isa P, Lopez S. Molecular anatomy of 2009 influenza virus A (H1N1). Arch Med Res 2009;40:643-54.  Back to cited text no. 7
    
8.
Gong J, Xu W, Zhang J. Structure and functions of influenza virus neuraminidase. Curr Med Chem 2007;14:113-22.  Back to cited text no. 8
    
9.
Joseph NV. Development of Neuraminidase Inhibitors as Anti-Influenza Virus Drugs. Drug Dev Res 1999;46:176-96.  Back to cited text no. 9
    
10.
Xu X, Zhu X, Dwek RA, Stevens J, Wilson IA. Structural characterization of the 1918 influenza virus H1N1 neuraminidase. J Virol 2008;82:10493-501.  Back to cited text no. 10
    
11.
Bauer K, Richter M, Wutzler P, Schmidtke M. Different neuraminidase inhibitor susceptibilities of human H1N1, H1N2, and H3N2 influenza A viruses isolated in Germany from 2001 to 2005/2006. Antiviral Res 2009;82:34-41.  Back to cited text no. 11
    
12.
Masukawa KM, Kollman PA, Kuntz ID. Investigation of neuraminidase-substrate recognition using molecular dynamics and free energy calculations. J Med Chem 2003;46:5628-37.  Back to cited text no. 12
    
13.
Hong AK, Peg MS, von IM. Influenza virus sialidase: Effect of calcium on steady-state kinetic parameters. Biochim Biophys Acta 1991;1077:65-71.  Back to cited text no. 13
    
14.
Wang SQ, Du QS, Huang RB, Zhang DW, Chou KC. Insights from investigating the interaction of oseltamivir (Tamiflu) with neuraminidase of the 2009 H1N1 swine flu virus Biochem Biophys Res Commun 2009;386:432-6.  Back to cited text no. 14
    
15.
Okomo-Adhiambo M, Nguyen HT, Sleeman K, Sheu TG, Deyde VM, Garten RJ, et al. Host cell selection of influenza neuraminidase variants: Implications for drug resistance monitoring in A (H1N1) viruses. Antiviral Res 2010;85:381-8.  Back to cited text no. 15
    
16.
Baranovich T, Saito R, Suzuki Y, Zaraket H, Dapat C, Caperig-Dapat I, et al. Emergence of H274Y oseltamivir-resistant A (H1N1) influenza viruses in Japan during the 2008-2009 season. J Clin Virol 2010;47:23-8.  Back to cited text no. 16
    
17.
Roschek B Jr, Fink RC, McMichael MD, Li D, Alberte RS. Elderberry flavonoids bind to and prevent H1N1 infection in vitro. Phytochemistry 2009;70:1255-61.  Back to cited text no. 17
    
18.
Mercader AG, Pomilio AB. QSAR study of flavonoids and biflavonoids as influenza H1N1 virus neuraminidase inhibitors. Eur J Med Chem 2010;45:1724-30.  Back to cited text no. 18
    
19.
Ives JA, Carr JA, Mendel DB, Tai CY, Lambkin R, Kelly L, et al. The H274Y mutation in the influenza A/H1N1 neuraminidase active site following oseltamivir phosphate treatment leave virus severely compromised both in vitro and in vivo. Antiviral Res 2002;55:307-17.  Back to cited text no. 19
    
20.
Monajjemi M, Mahdavian L, Mollaamin F. Characterization of nanocrystalline cylicon germanium film and nanotube in adsoption gas by Monte Carlo and langevin dynamic simulation. Bull Chem Soc Ethiop Bull Chem Soc Ethiop 2008;22:227-86.  Back to cited text no. 20
    
21.
Lawrenz M, Wereszczynski J, Amaro R, Walker R, Roitberg A, McCammon JA. Impact of calcium on N1 influenza neuraminidase dynamics and binding free energy. Proteins 2010;78:2523-32.  Back to cited text no. 21
Advanced Biomedical Research
Volume 2015, october
October 2015
Pages 1-5