Figure S1. Hexokinase Type I Enzyme

Figure S1. Hexokinase type I enzyme

Figure S2. Schematic structure of GLU, G6P, PHE, PPA and PLA (l-r)

Figure S3. Hexokinase binding site located by molecular docking through AutodockVina

Figure S4. Superimpose of G6P of crystal structure and first pose of docked G6P

Table S1. ΔG (kcal/mol) for interaction of GLU, G6P, PHE, PPA and PLA with HK-I in 10 different poses obtained by GOLD molecular docking

Poses / Glu / G6P / Phe / PPA / PLA
1 / -19.4451 / -28.6129 / -22.5978 / -24.3898 / -21.7541
2 / -19.3174 / -28.7269 / -22.5541 / -23.6419 / -22.1501
3 / -19.311 / -28.1856 / -22.4995 / -24.2562 / -21.8809
4 / -18.952 / -26.4636 / -22.1573 / -22.7195 / -21.9851
5 / -18.6021 / -27.4635 / -22.1011 / -23.7252 / -21.7081
6 / -18.5547 / -24.2774 / -21.8715 / -23.9221 / -21.2518
7 / -18.1928 / -24.2339 / -21.389 / -23.2364 / -21.1265
8 / -17.8689 / -24.7306 / -21.2625 / -22.8084 / -21.8576
9 / -17.5414 / -27.5765 / -19.5162 / -23.3349 / -21.3132
10 / -16.4117 / -23.8572 / -18.0181 / -23.1389 / -18.628

Table S2. Score of energy interaction between ligands and HK_I

Ligand / MolDock Score (kJ/mol) / Rerank Score (kJ/mol)
Glu / -57.566 / -57.718
G6P / -77.864 / -71.535
Phe / -43.875 / -41.823
PPA / -61.29 / -55.858
PLA / -51.101 / -53.866

Table S3. Hydrogen bonds and Pi interactions in different complex of HK-I with G6P, PPA and PLA after molecular docking.

Ligand / H Bond / Pi Interaction
Residues/Atoms / Distance (Å) / Residues/Atoms / Distance (Å)
Phe / A:THR232:N - Phe:O18
A:THR232:OG1 - Phe:O18
A:SER415:N - Phe:O17
Phe:O17 - A:SER415:OG
Phe:N19 - A:SER88:OG / 2.79
2.85
2.93
2.74
3.02 / :Phe - A:ARG91:NH2
:Phe - A:ARG91:NH1 / 4.34
6.05
PPA / A:SER88:HN - :PPA:O19
A:SER88:HG - :PPA:O19
A:THR232:HN - :PPA:O18
A:SER415:HN - :PPA:O17 / 2.04
1.62
1.75
2.12 / :PPA - A:ARG91:NH2
:PPA - A:ARG91:NH1 / 4.68
6.03
PLA / A:SER88:HN - :PLA:O20
A:SER88:HG - :PLA:O20
A:THR232:HN - :PLA:O17
:PLA:H18 - A:SER415:OG / 1.79
1.83
1.98
1.91 / :PLA - A:ARG91:NH2
:PLA - A:ARG91:NH1 / 3.99
5.58
GLU / A:SER88:OG - GLU:O8
A:LYS173:NZ - GLU:O12
A:THR232:N - GLU:O11
A:SER415:N - GLU:O7
A:SER415:OG - GLU:O7
GLU:H21 - A:SER88:OG
GLU:H23 - A:ASP209:OD2
GLU:H24 - A:ASP209:OD2 / 3.12
3.11
2.94
3.12
2.80
2.17
1.79
2.02
G6P / A:SER88:HN - :G6P:O15
A:SER88:HG - :G6P:O15
A:THR232:HN - :G6P:O14
A:SER415:HN - :G6P:O16
A:THR449:HN - :G6P:O8
:G6P:H24 - A:ASP413:OD2
:G6P:H25 - A:ASP84:OD2
:G6P:H26 - A:ASP84:OD1
:G6P:H27 - A:ASP209:OD2 / 2.06
1.72
1.89
2.05
1.83
1.96
1.73
2.26
1.93

Table S4. Interactions between HK residues and Glu in average structure of the complex

HK-Glu Residues& Atoms / Distance / Category / Type
:THR226:H / :GLU459:O1 / 2.21432 / Hydrogen Bond / Conventional Hydrogen Bond
:GLU459:H10 / :SER149:OG / 2.29762 / Hydrogen Bond / Conventional Hydrogen Bond
:GLU459:H6 / :ASP203:OD2 / 1.77916 / Hydrogen Bond / Conventional Hydrogen Bond
:GLU459:H5 / :THR226:O / 2.49653 / Hydrogen Bond / Carbon Hydrogen Bond

Table S5. Interactions between HK residues and G6P in average structure of the complex

HK-G6P Residues& Atoms / Distance / Category / Type
:LYS412:NZ / :G6P459:O3P / 5.31443 / Electrostatic / Attractive Charge
:SER88:H / :G6P459:O2P / 1.98077 / Hydrogen Bond / Conventional Hydrogen Bond
:SER88:HG / :G6P459:O2P / 1.54215 / Hydrogen Bond / Conventional Hydrogen Bond
:LYS167:HZ3 / :G6P459:O4 / 1.91334 / Hydrogen Bond / Conventional Hydrogen Bond
:THR226:H / :G6P459:O6 / 1.8742 / Hydrogen Bond / Conventional Hydrogen Bond
:THR226:HG1 / :G6P459:O1P / 1.72849 / Hydrogen Bond / Conventional Hydrogen Bond
:SER409:H / :G6P459:O3P / 1.87854 / Hydrogen Bond / Conventional Hydrogen Bond
:SER409:HG / :G6P459:O3P / 1.62939 / Hydrogen Bond / Conventional Hydrogen Bond
:G6P459:H8 / :ASP407:OD1 / 1.80601 / Hydrogen Bond / Conventional Hydrogen Bond
:G6P459:H9 / :ASP84:OD1 / 1.8615 / Hydrogen Bond / Conventional Hydrogen Bond

Table S6. Interactions between HK residues and Phe in average structure of the complex

HK-Phe Residues& Atoms / Distance / Category / Type
:GLY87:H / :PHA459:N / 2.81099 / Hydrogen Bond / Conventional Hydrogen Bond
:THR226:H / :PHA459:O1 / 2.05353 / Hydrogen Bond / Conventional Hydrogen Bond
:THR226:HG1 / :PHA459:O1 / 2.19282 / Hydrogen Bond / Conventional Hydrogen Bond
:GLY227:H / :PHA459:O1 / 2.06155 / Hydrogen Bond / Conventional Hydrogen Bond
:GLY87:HA2 / :PHA459:O / 2.92044 / Hydrogen Bond / Carbon Hydrogen Bond
:THR226:HB / :PHA459:O1 / 2.7363 / Hydrogen Bond / Carbon Hydrogen Bond
:GLY87:H / :PHA459 / 2.43354 / Hydrogen Bond / Pi-Donor Hydrogen Bond
:PHA459 / :LYS167 / 5.12444 / Hydrophobic / Pi-Alkyl

Table S7. Interactions between HK residues and PPA in average structure of the complex

HK-PPA Residues& Atoms / Distance / Category / Type
:SER88:H / :PPA459:O1 / 1.96816 / Hydrogen Bond / Conventional Hydrogen Bond
:THR226:H / :PPA459:O2 / 1.87412 / Hydrogen Bond / Conventional Hydrogen Bond
:GLY87:HA2 / :PPA459:O1 / 2.63483 / Hydrogen Bond / Carbon Hydrogen Bond
:GLY87:HA3 / :PPA459:O1 / 2.93735 / Hydrogen Bond / Carbon Hydrogen Bond
:GLY225:HA3 / :PPA459:O2 / 2.40452 / Hydrogen Bond / Carbon Hydrogen Bond
:THR226:HB / :PPA459:O2 / 2.73295 / Hydrogen Bond / Carbon Hydrogen Bond
:PPA459 / :LYS167 / 4.36675 / Hydrophobic / Pi-Alkyl
:PPA459 / :ILE223 / 4.45665 / Hydrophobic / Pi-Alkyl

Table S8. Interactions between HK residues and PLA in average structure of the complex

HK-PLA Residues& Atoms / Distance / Category / Type
:THR226:H / :PLA459:O1 / 1.91844 / Hydrogen Bond / Conventional Hydrogen Bond
:SER409:H / :PLA459:O1 / 2.39846 / Hydrogen Bond / Conventional Hydrogen Bond
:SER409:H / :PLA459:O2 / 2.94754 / Hydrogen Bond / Conventional Hydrogen Bond
:PLA459:H8 / :THR226:OG1 / 1.57486 / Hydrogen Bond / Conventional Hydrogen Bond
:PLA459:H10 / :ASP407:OD2 / 1.90782 / Hydrogen Bond / Conventional Hydrogen Bond
:GLY87:HA3 / :PLA459:O / 2.80299 / Hydrogen Bond / Carbon Hydrogen Bond
:GLY225:HA3 / :PLA459:O1 / 2.6956 / Hydrogen Bond / Carbon Hydrogen Bond
:GLY408:HA2 / :PLA459:O1 / 2.46479 / Hydrogen Bond / Carbon Hydrogen Bond
:PLA459 / :ILE223 / 5.34121 / Hydrophobic / Pi-Alkyl

Table S9. Hydrogen bond analysis during the course of MD simulations for the complexes

Complex / Donor / Acceptor / %Occupied / Distance / Angle
HK-I_GLU / 459:O4 / 149:OH / 53.54 / 3.265 ( 0.18) / 120.00 (29.93)
459:OP / 226:OH / 99.91 / 2.639 ( 0.11) / 13.92 ( 8.45)
HK-I_G6P / 459:O4 / 167:NZ / 93.21 / 3.045 ( 0.19) / 96.21 (37.80)
459:O2 / 91:NH2 / 65.36 / 3.141 ( 0.18) / 127.10 (10.94)
HK-I_Phe / 459:O / 226:OH / 31.37 / 3.204 ( 0.20) / 73.36 (34.41)
459:O1 / 88:OH / 44.84 / 3.186 ( 0.19) / 126.76 (23.83)
HK-I_PLA / 459:O / 409:OH / 28.00 / 3.289 ( 0.15) / 107.51 (18.61)
459:O / 226:OH / 25.59 / 3.271 ( 0.16) / 114.18 (20.67)
459:O / 226:OH / 91.72 / 2.803 ( 0.16) / 146.37 (11.37)
HK-I_PPA / 459:O1 / 226:OH / 85.33 / 3.216 ( 0.16) / 138.17 (15.53)
459:O / 88:OH / 60.04 / 3.182 ( 0.20) / 102.83 (33.64)