Supplementary material
A 3D-RISM/RISM study of the oseltamivir binding efficiency with the wild-type and
resistance-associated mutant forms of the viral influenza B neuraminidase
1
Jiraphorn Phanich, Thanyada Rungrotmongkol,
4
2,*
5
Phongphanphanee, Norio Yoshida, Fumio Hirata,
3
Daniel Sindhikara, Saree
6,*
7
Nawee Kungwan and Supot
1
Hannongbua
1
Computational Chemistry Unit Cell, Department of Chemistry, Faculty of Science,
Chulalongkorn University, 254 Phayathai Road, Bangkok 10330, Thailand
2
Department of Biochemistry, Faculty of Science, Chulalongkorn University, 254
Phayathai Road, Bangkok 10330, Thailand
3
4
Schrödinger, Inc., 120 West 45th Street, 17th Floor, New York, New York 10036
Department of Materials Science, Faculty of Science, Kasetsart University, 50
Ngamwongwan Road, Bangkok 10900, Thailand
5
Department of Chemistry, Graduate School of Sciences, Kyushu University, Fukuoka
812-8581, Japan
6
College of Life Sciences, Ritsumeikan University, and Molecular Design Frontier Co.
Ltd., Kusatsu 525-8577, Japan
7
Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai
50200, Thailand
*Corresponding authors:
Dr.Thanyada Rungrotmongkol, phone: +66 22187602, fax: +66 22187603, e-mail:
t.rungrotmongkol@gmail.com;
Prof. Dr. Fumio Hirata, e-mail: hirataf@fc.ritsumei.ac.jp.
S1
Content
Page
Table S1. Amino acid sequence alignment of the neuraminidase catalytic
sites (bold font), framework sites and nearby framework sites
(underlined) between three different influenza A viruses and the influenza
B Beijing strain virus………………………………………………………
S3
Table S2. The genetic (amino acid sequence identity and similarity) and
structural (RMSD) relationship between neuraminidases of three
influenza A strains compared to the Beijing influenza B
virus………………………………..............................................................
S4
Figure S1. The RMSD plot for all the neuraminidase protein atoms
versus simulation time of the (a) wild-type and the (b) E119G, (C)
R152K and (d) D198N single mutations, simulated with three different
starting velocities (black, dark grey and light grey)……………………….
S5
Figure S2. The time-dependence of the distance between the functional
group of oseltamivir and the influenza B neuraminidase residues in the
(a) wild-type and the (b) E119G, (c) R152K and (d) D198N single
substitution mutations……………………………………………………..
S6
Figure S3. The distribution of dihedral angle over the 15 ns of production
phase for bulky group side chain of oseltamivir in free form (a), and
complex form (b) with bound to wild-type, E119G, R152K and D198N
neuraminidase mutation.
S7
Cover artwork
S2
N2 numbering
118
119
151
152
156
178
179
198
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274
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347
371
405
406
425
Table S1. Amino acid sequence alignment of the neuraminidase catalytic sites (bold
font), framework sites and nearby framework sites (underlined) between three different
influenza A viruses and the influenza B Beijing strain virus
B/Beijing
R E D R R W S D I R E H E E R N G R W Y E
A/pH1N1
R E D R R W S D I R E H E E R N N R G Y E
A/H5N1
R E D R R W S D I R E H E E R N Y R G Y E
A/H2N2
R E D R R W S D I R E H E E R N Q R G Y E
S3
Table S2. The genetic (amino acid sequence identity and similarity) and structural
(RMSD) relationship between neuraminidases of three influenza A strains compared to
the Beijing influenza B virus.
Influenza Ba
a
H5N1c
H2N2d
Sequence identity (%)
34
33
31
Sequence similarity (%)
54
53
49
RMSD (Å)
2.3
2.3
2.3
B/Beijing/1/87 strain, 1NSC.pdb
b
c
pH1N1b
A/California/4/2009 strain, 3TI6.pdb
A/Vietnam/1203 strain, 2HU4.pdb
d
A/Tokyo/3/1967 strain, 2BAT.pdb
S4
Figure S1. The RMSD plot for all the neuraminidase protein atoms versus simulation
time of the (a) wild-type and the (b) E119G, (C) R152K and (d) D198N single mutations,
simulated with three different starting velocities (black, dark grey and light grey).
S5
Figure S2. The time-dependence of the distance between the functional group of
oseltamivir and the influenza B neuraminidase residues in the (a) wild-type and the (b)
E119G, (c) R152K and (d) D198N single substitution mutations.
S6
Figure S3. The distribution of dihedral angle over the 15 ns of production phase for
bulky group side chain of oseltamivir in free form (a), and complex form (b) with bound
to wild-type, E119G, R152K and D198N neuraminidase mutation.
S7
"For consideration for use on the cover"