Fig 1.
Molecular structures of catechins.
Molecular structures of catechins in the tea polyphenol. EGCG: R2 is OH, R1 is G; ECG: R2 is H, R1 is G; EGC: R1 and R2 are OH; EC: R1 is OH, R2 is H.
Table 1.
Molecular dynamics simulation settings.
Table 2.
The binding affinity from semi-flexible docking (kcal/mol) and the possibility (in parenthesis) of four types of catechins and their chemical groups binding to the S1 pocket of trypsin.
Fig 2.
Estimation of MD simulation equilibration and analysis of the stability of protein structure.
Time evolutions of a) the backbone RMSD and b) the radius of gyration (Rg) of trypsin in MD simulations. Black color indicates trypsin in catechin-free form; red, blue, dark-cyan and magenta indicate trypsin in the complex with EC, ECG, EGC and EGCG, respectively.
Fig 3.
Characterization of residues flexibility.
The Cα B-factor for each residue in trypsin computed from MD simulation trajectories in the form of catechin-free (black) and complex with EC (red), ECG (blue), EGC (dark-cyan) and EGCG (magenta), respectively. The orange line represents the Cα B-factor from PDB file. The wiring diagram shows the secondary structure of trypsin. The bar chart at the bottom of picture shows the distance range of the Cα atom to the nearest heavy atom of catechins. The inset enlarges the sequence motifs in the S1 pocket.
Fig 4.
Representative trypsin-catechin complex structures.
Representative structure models clustered from MD simulation trajectories for trypsin complex with a) EC, b) EGC, c) ECG and d) EGCG. Catechins are shown as ball-and-stick model, trypsin as cartoon. The catalytic triad (Asp102, His57, Ser195) is shown in stick. Residues interact with catechins by hydrogen bond and hydrophobic interaction highlighted by lines.
Fig 5.
Characterization of the conformation changes of catechins.
The distances among the rings of catechins in the optimized structure (a, b, c and d) and their average distances calculated from MD trajectories (a′, b′, c′ and d′). (a and a′) EC; (b and b′) EGC; (c and c′) ECG; (d and d′) EGCG.
Table 3.
Binding free energies (kcal/mol) and the energy components for catechins with different structures, orientations and stereoisomers.
Fig 6.
Analysis of contributions of each component in binding free energy.
Comparison of the binding free energy components of trypsin binding with EC (red), EGC (blue), ECG (dark cyan) and EGCG (magenta).
Fig 7.
Analysis of contributions of each residue in binding free energy.
Binding free energies contributed from each residue to stabilize the trypsin-catechin complex. Residues with ΔGper-decomp ≥ 1.0 kcal/mol were labeled. (a) trypsin-EC; (b) trypsin-EGC; (c) trypsin-ECG; and (d) trypsin-EGCG.