532
S. von Grafenstein et al.
13. Lindorff-Larsen K, Piana S, Palmo K, Maragakis P, Klepeis JL, Dror RO, Shaw DE (2010)
Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins: Str,
Funct, Bioinform 78(8):1950–1958. doi:10.1002/prot.22711
14. Klepeis JL, Lindorff-Larsen K, Dror RO, Shaw DE (2009) Long-timescale molecular dynamics simulations of protein structure and function. Curr Opin Struct Biol 19(2):120–127.
doi:10.1016/j.sbi.2009.03.004
15. Goetz AW, Williamson MJ, Xu D, Poole D, Le Grand S, Walker RC (2012) Routine microsecond molecular dynamics simulations with AMBER on GPUs. 1. generalized born. J Chem
Theory Comput 8(5):1542–1555. doi:10.1021/ct200909j
16. Luque I, Freire E (2000) Structural stability of binding sites: Consequences for binding affinity and allosteric effects. Proteins: Str Funct Genet 41(S4):63–71. doi:10.1002/1097-0134
(2000) 41:4+<63::AID-PROT60>3.0.CO;2-6
17. Kroemer RT (2007) Structure-based drug design: docking and scoring. Curr Protein Pept Sci
8(4):312–328
18. B-Rao C, Subramanian J, Sharma SD (2009) Managing protein flexibility in docking and its
applications. Drug Discov Today 14(7–8):394–400. doi:10.1016/j.drudis.2009.01.003
19. Jiang F, Kim SH (1991) Soft docking-matching of molecular—surface cubes. J Mol Biol
219(1):79–102. doi:10.1016/0022-2836(91)90859-5
20. Claussen H, Buning C, Rarey M, Lengauer T (2001) FlexE: efficient molecular docking considering protein structure variations. J Mol Biol 308(2):377–395. doi:10.1006/jmbi.2001.4551
21. Flick J, Tristram F, Wenzel W (2012) Modeling loop backbone flexibility in receptor-ligand
docking simulations. J Comput Chem 33(31):2504–2515. doi:10.1002/jcc.23087
22. Cozzini P, Kellogg GE, Spyrakis F, Abraham DJ, Costantino G, Emerson A, Fanelli F, Gohlke
H, Kuhn LA, Morris GM, Orozco M, Pertinhez TA, Rizzi M, Sotriffer CA (2008) Target flexibility: an emerging consideration in drug discovery and design. J Med Chem 51(20):6237–
6255. doi:10.1021/jm800562d
23. Gamblin SJ, Skehel JJ (2010) influenza hemagglutinin and neuraminidase membrane glycoproteins. J Biol Chem 285(37):28403–28409. doi:10.1074/jbc.R110.129809
24. Lill MA (2011) Efficient incorporation of protein flexibility and dynamics into molecular
docking simulations. Biochemistry 50(28):6157–6169. doi:10.1021/bi2004558
25. Russell RJ, Haire LF, Stevens DJ, Collins PJ, Lin YP, Blackburn GM, Hay AJ, Gamblin SJ,
Skehel JJ (2006) The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design. Nature 443(7107):45–49. doi:10.1038/nature05114
26. Cheng LS, Amaro RE, Xu D, Li WW, Arzberger PW, McCammon JA (2008) Ensemble-based
virtual screening reveals potential novel antiviral compounds for avian influenza neuraminidase. J Med Chem 51(13):3878–3894. doi:10.1021/jm8001197
27. Grienke U, Schmidtke M, Kirchmair J, Pfarr K, Wutzler P, Durrwald R, Wolber G, Liedl KR,
Stuppner H, Rollinger JM (2010) Antiviral Potential and Molecular Insight into Neuraminidase Inhibiting Diarylheptanoids from Alpinia katsumadai. J Med Chem 53(2):778–786.
doi:10.1021/jm901440f
28. Vavricka CJ, Li Q, Wu Y, Qi JX, Wang MY, Liu Y, Gao F, Liu J, Feng EG, He JH, Wang JF,
Liu H, Jiang HL, Gao GF (2011) Structural and functional analysis of laninamivir and its octanoate prodrug reveals group specific mechanisms for influenza NA inhibition. PloS Pathog
7(10):e1002249. doi:10.1371/journal.ppat.1002249
29. Li Q, Qi JX, Zhang W, Vavricka CJ, Shi Y, Wei JH, Feng EG, Shen JS, Chen JL, Liu D, He JH,
Yan JH, Liu H, Jiang HL, Teng MK, Li XB, Gao GF (2010) The 2009 pandemic H1N1 neuraminidase N1 lacks the 150-cavity in its active site. Nat Struct Mol Biol 17(10):1266–1268.
doi:10.1038/nsmb.1909
30. van der Vries E, Collins PJ, Vachieri SG, Xiong XL, Liu JF, Walker PA, Haire LF, Hay
AJ, Schutten M, Osterhaus A, Martin SR, Boucher CAB, Skehel JJ, Gamblin SJ (2012)
H1N1 2009 Pandemic influenza virus: Resistance of the I223R neuraminidase mutant explained by kinetic and structural analysis. PloS Pathog 8(9):e1002914. doi:10.1371/journal.
ppat.1002914
S. von Grafenstein et al.
13. Lindorff-Larsen K, Piana S, Palmo K, Maragakis P, Klepeis JL, Dror RO, Shaw DE (2010)
Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins: Str,
Funct, Bioinform 78(8):1950–1958. doi:10.1002/prot.22711
14. Klepeis JL, Lindorff-Larsen K, Dror RO, Shaw DE (2009) Long-timescale molecular dynamics simulations of protein structure and function. Curr Opin Struct Biol 19(2):120–127.
doi:10.1016/j.sbi.2009.03.004
15. Goetz AW, Williamson MJ, Xu D, Poole D, Le Grand S, Walker RC (2012) Routine microsecond molecular dynamics simulations with AMBER on GPUs. 1. generalized born. J Chem
Theory Comput 8(5):1542–1555. doi:10.1021/ct200909j
16. Luque I, Freire E (2000) Structural stability of binding sites: Consequences for binding affinity and allosteric effects. Proteins: Str Funct Genet 41(S4):63–71. doi:10.1002/1097-0134
(2000) 41:4+<63::AID-PROT60>3.0.CO;2-6
17. Kroemer RT (2007) Structure-based drug design: docking and scoring. Curr Protein Pept Sci
8(4):312–328
18. B-Rao C, Subramanian J, Sharma SD (2009) Managing protein flexibility in docking and its
applications. Drug Discov Today 14(7–8):394–400. doi:10.1016/j.drudis.2009.01.003
19. Jiang F, Kim SH (1991) Soft docking-matching of molecular—surface cubes. J Mol Biol
219(1):79–102. doi:10.1016/0022-2836(91)90859-5
20. Claussen H, Buning C, Rarey M, Lengauer T (2001) FlexE: efficient molecular docking considering protein structure variations. J Mol Biol 308(2):377–395. doi:10.1006/jmbi.2001.4551
21. Flick J, Tristram F, Wenzel W (2012) Modeling loop backbone flexibility in receptor-ligand
docking simulations. J Comput Chem 33(31):2504–2515. doi:10.1002/jcc.23087
22. Cozzini P, Kellogg GE, Spyrakis F, Abraham DJ, Costantino G, Emerson A, Fanelli F, Gohlke
H, Kuhn LA, Morris GM, Orozco M, Pertinhez TA, Rizzi M, Sotriffer CA (2008) Target flexibility: an emerging consideration in drug discovery and design. J Med Chem 51(20):6237–
6255. doi:10.1021/jm800562d
23. Gamblin SJ, Skehel JJ (2010) influenza hemagglutinin and neuraminidase membrane glycoproteins. J Biol Chem 285(37):28403–28409. doi:10.1074/jbc.R110.129809
24. Lill MA (2011) Efficient incorporation of protein flexibility and dynamics into molecular
docking simulations. Biochemistry 50(28):6157–6169. doi:10.1021/bi2004558
25. Russell RJ, Haire LF, Stevens DJ, Collins PJ, Lin YP, Blackburn GM, Hay AJ, Gamblin SJ,
Skehel JJ (2006) The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design. Nature 443(7107):45–49. doi:10.1038/nature05114
26. Cheng LS, Amaro RE, Xu D, Li WW, Arzberger PW, McCammon JA (2008) Ensemble-based
virtual screening reveals potential novel antiviral compounds for avian influenza neuraminidase. J Med Chem 51(13):3878–3894. doi:10.1021/jm8001197
27. Grienke U, Schmidtke M, Kirchmair J, Pfarr K, Wutzler P, Durrwald R, Wolber G, Liedl KR,
Stuppner H, Rollinger JM (2010) Antiviral Potential and Molecular Insight into Neuraminidase Inhibiting Diarylheptanoids from Alpinia katsumadai. J Med Chem 53(2):778–786.
doi:10.1021/jm901440f
28. Vavricka CJ, Li Q, Wu Y, Qi JX, Wang MY, Liu Y, Gao F, Liu J, Feng EG, He JH, Wang JF,
Liu H, Jiang HL, Gao GF (2011) Structural and functional analysis of laninamivir and its octanoate prodrug reveals group specific mechanisms for influenza NA inhibition. PloS Pathog
7(10):e1002249. doi:10.1371/journal.ppat.1002249
29. Li Q, Qi JX, Zhang W, Vavricka CJ, Shi Y, Wei JH, Feng EG, Shen JS, Chen JL, Liu D, He JH,
Yan JH, Liu H, Jiang HL, Teng MK, Li XB, Gao GF (2010) The 2009 pandemic H1N1 neuraminidase N1 lacks the 150-cavity in its active site. Nat Struct Mol Biol 17(10):1266–1268.
doi:10.1038/nsmb.1909
30. van der Vries E, Collins PJ, Vachieri SG, Xiong XL, Liu JF, Walker PA, Haire LF, Hay
AJ, Schutten M, Osterhaus A, Martin SR, Boucher CAB, Skehel JJ, Gamblin SJ (2012)
H1N1 2009 Pandemic influenza virus: Resistance of the I223R neuraminidase mutant explained by kinetic and structural analysis. PloS Pathog 8(9):e1002914. doi:10.1371/journal.
ppat.1002914