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Bioinformatics,Research,Group,,Department,of,Chemistry,,Faculty,of,Mathematics,and,Science,,University,of,Indonesia,

1,

Designing Cyclopentapeptide Inhibitor of Neuraminidase H5N1 Virus through Molecular and pharmacology Simulation

Usman Sumo Friend Tambunan*, Arli Aditya Parikesit, Yossy Carolina Unadi,

Djati Kerami Department of Chemistry, Faculty of Mathematics and Sciences, University of

Indonesia Depok 16424

(*) Corresponding author: usman@ui.ac.id

Table S1. Contact residue of the ligandd during molecular dynamics at 310 K

Ligand

steps CLDRC CILRC CIWRC

Beginning of

Initialization

Glu99, Glu99, Arg132,

Arg136, Trp159,

Ser227, Glu258,

Tyr324, Arg348,

Arg348, Arg384

Thr128, Arg273,

Tyr324, Arg348

Arg98, Glu99,

Glu99, Glu99,

Thr115, Thr115,

Tyr324, Arg348,

Arg348

The end of

Initialization

Glu99, Glu99, Arg132,

Arg136, Trp159,

Ser227, Glu258,

Tyr324, Arg348,

Arg348, Arg384

Thr128, Arg273,

Tyr324, Arg348,

Tyr382

Arg98, Glu99,

Glu99, Glu99,

Thr115, Thr115,

Tyr324, Arg348,

Arg348

Production of

5000

picosecond

Arg98, Glu99, Glu99,

Glu99, Asp131,

Asp131, Arg132,

Arg132, Arg136,

Trp159, Glu208,

Ser227, Glu258,

Glu258, Arg273,

Arg273, Tyr324,

Arg348, Arg348,

Tyr382

Glu257, Glu258,

Glu258, Arg273,

Lys412

Arg98, Glu99,

Glu99, Glu99,

Thr115, Arg136,

Ala158, Trp159,

Asp179, Arg273,

Tyr324, Arg348,

Arg348

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2,

Cooling

Arg98, Glu99, Glu99,

Glu99, Asp131,

Asp131, Arg132,

Arg132, Arg136,

Trp159, Glu208,

Ser227, Glu258,

Glu258, Arg273,

Arg273, Tyr324,

Arg348, Arg348,

Tyr382

Glu257, Glu258,

Glu258, Arg273,

Lys412

Arg98, Glu99,

Glu99, Glu99,

Thr115, Arg136,

Ala158, Trp159,

Asp179, Arg273,

Tyr324, Arg348,

Arg348

Note : Residues in red are the active sites of NA

Table S2. The comparison between contact residue and hydrogen bond

during and after the molecular dynamics simulation at 310 K

Ligand

Simulation

LDR ILR IWR

Molecular

docking

Glu99, Glu99, Glu99,

Arg132, Arg136, Trp159,

Tyr324, Arg348, Tyr382,

Tyr382

Arg98, Thr128,

Arg132, Arg 273,

Asn275, Arg348

Glu99, Glu99,

Glu257, Glu258,

Arg348

Molecular

dynamics 310

K

Arg98, Glu99, Glu99,

Glu99, Asp131, Asp131,

Arg132, Arg132, Arg136,

Trp159, Glu208, Ser227,

Glu258, Glu258, Arg273,

Arg273, Tyr324, Arg348,

Arg348, Tyr382

Glu257, Glu258,

Glu258, Arg273,

Lys412

Arg98, Glu99,

Glu99, Glu99,

Thr115, Arg136,

Ala158, Trp159,

Asp179, Arg273,

Tyr324, Arg348,

Arg348

Note : Residues in red are the active sites of NA

Table S3. Contact residue of molecular dynamics ligand simulation at 312 K

Ligand Steps CLDRC CILRC CIWRC

Beginning of Glu99, Glu99, Glu99, Glu99, Arg98, Glu99,

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3,

Initialization Arg132, Arg136, Trp159, Ser227, Tyr324, Arg348, Tyr382

Arg132, Arg136, Trp159,Ser227 Tyr324, Arg348, Tyr382

Glu99, Glu99, Thr115, Thr115, Tyr324, Arg348, Arg348

The end of Initialization

Glu99, Glu99, Arg132, Arg136, Trp159, Ser227, Tyr324, Arg348, Tyr382

Glu99, Glu99, Arg132, Trp159, Glu208, Tyr324, Arg348, Arg348, Tyr382, Glu405, Glu405

Glu99, Asp131, Glu208, Arg273, Arg273, Asn275, Arg348, Arg410

Production of 5000 ps

Arg98, Glu99, Arg132, Arg136, Glu208, Ser227, Ser227, Glu258, Arg273, Tyr382, Glu405, Arg410

Glu99, Glu99, Arg132, Trp159, Glu208, Tyr324, Arg348, Arg348, Tyr382, Glu405, Glu405

Arg98, Glu99, Asp131, Glu208, Glu208, Tyr382

Cooling

Arg98, Glu99, Glu99, Arg132, Arg136, Ser160, Glu208, Ser227, Glu258, Arg273, Tyr382, Glu405, Glu405, Arg410, Arg410

Glu99, Arg132, Arg132, Ser160, Glu208, Ser227, Arg273, Arg273, Asn275, Arg348, Arg348, Tyr382, Tyr382, Glu405, Glu405, Lys412

Glu99, Asp131, Glu208, Glu208, Trp276, Arg348, Tyr382, Tyr382, Arg410

Note : Residues in red are the active sites of NA

Table S4. Comparison of the formed contact residue and hydrogen bond

during molecular docking and dynamics at 312 K

Ligand

Simulation

CLDRC CILRC CIWRC

Molecular Docking Arg98, Glu99,

Arg132, Arg136,

Glu208, Ser227,

Ser227, Glu258,

Arg273, Tyr382,

Glu405, Arg410

Glu99, Glu99,

Arg132, Trp159,

Glu208, Tyr324,

Arg348, Arg348,

Tyr382, Glu405,

Glu405

Arg98, Glu99,

Asp131, Glu208,

Glu208, Tyr382

Molecular

Dynamics 312 K

Arg98, Glu99,

Arg132, Arg136,

Glu99, Glu99,

Arg132, Trp159,

Arg98, Glu99,

Asp131, Glu208,

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Bioinformatics,Research,Group,,Department,of,Chemistry,,Faculty,of,Mathematics,and,Science,,University,of,Indonesia,

4,

Glu208, Ser227,

Glu258, Arg273,

Tyr382, Glu405,

Arg410

Glu208, Tyr324,

Arg348, Arg348,

Tyr382, Glu405,

Glu405

Glu208, Tyr382

Note : Residues in red are the active sites of NA

a)

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Bioinformatics,Research,Group,,Department,of,Chemistry,,Faculty,of,Mathematics,and,Science,,University,of,Indonesia,

5,

b)

Figure S1. The visualization of active side residue interactions of Ligand CLDRC during the beginning pf initialisation stage (a) Temperature of 310K and (b) Temperature of 312K

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6,

a)

b)

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7,

Figure S2. The visualisation of active side residue interactions of CLDRC ligand during the end of initialisation stage(a) Temperature of 310K and (b) Temperature of 312K

a)

Supplementary,materials,,

Bioinformatics,Research,Group,,Department,of,Chemistry,,Faculty,of,Mathematics,and,Science,,University,of,Indonesia,

8,

b)

Figure S3. Visualisation of active side residue interactions of CLDRC ligand during production stage (a) Temperature of 310K and (b) Temperature of 312K

Supplementary,materials,,

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9,

a)

Supplementary,materials,,

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10,

b)

Figure S4. The visualisation of active site residue interactions of CLDRC ligand during cooling stage. (a) Temperature of 310K and (b) Temperature of 312K

.

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11,

a)

b)

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12,

Figure S5. The visualisation of active site resiude interactions of CILRC ligand during the beginning of initialisation stage (a) Temperature of 310K and (b) Temperature of 312K

a)

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Bioinformatics,Research,Group,,Department,of,Chemistry,,Faculty,of,Mathematics,and,Science,,University,of,Indonesia,

13,

b)

Figure S6. The visualisation of active side interactions of CILRC ligand during the end of initialisation stage (a) Temperature of 310K and (b)Temperature of 312K

Supplementary,materials,,

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14,

a)

b)

Supplementary,materials,,

Bioinformatics,Research,Group,,Department,of,Chemistry,,Faculty,of,Mathematics,and,Science,,University,of,Indonesia,

15,

Figure S7. The visualisation of active site residue interactions of CILRC

ligand during production stage (a) Temperature of 310K and (b) Temperature of 312K

a)

Supplementary,materials,,

Bioinformatics,Research,Group,,Department,of,Chemistry,,Faculty,of,Mathematics,and,Science,,University,of,Indonesia,

16,

b)

Figure S8. The visualisation of active site residue interactions of CILRC ligand during cooling stage (a) Temperature of 310K dan (b) Temperature of 312K

Supplementary,materials,,

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17,

a)

Supplementary,materials,,

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18,

b)

Figure S9. The visualisation of active site residue interactions of CIWRC

ligand during the beginning of initialisation stage. (a)

Temperature of 310K and (b) Temperature of 312K

Supplementary,materials,,

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19,

a)

b)

Supplementary,materials,,

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20,

Figure S10. The visualisation of active site residue interactions of CIWRC

ligand during the end of the initialisation stage (a)

Temperature of 310K and (b) Temperature of 312K

a)

Supplementary,materials,,

Bioinformatics,Research,Group,,Department,of,Chemistry,,Faculty,of,Mathematics,and,Science,,University,of,Indonesia,

21,

b)

Figure S11. The visualisation of active site residue interactions of CIWRC

ligand during the production stage (a) Temperature of 310K and (b)

Temperature of 312K

Supplementary,materials,,

Bioinformatics,Research,Group,,Department,of,Chemistry,,Faculty,of,Mathematics,and,Science,,University,of,Indonesia,

22,

a)

b)

Supplementary,materials,,

Bioinformatics,Research,Group,,Department,of,Chemistry,,Faculty,of,Mathematics,and,Science,,University,of,Indonesia,

23,

Figure S12. The visualisation of active site residue interactions of CIWRC

ligand during the cooling stage (a) Temperature of 310K and (b)

Temperature of 312K