Figure 1.
Conformational association of an energetically favored ligand and specific target.
The ligand is associated to the specific target with hydrogen bonds and hydrophobic interactions inferring the biological activity of compounds. (A) The hypothetical model where the ligand is forming hydrogen bonds to target. (B) The ligand is associated with hydrophobic interactions. (Ci) target is modified. (Cii) ligand is modified. (Ciii) ligand is allied with metal-associated hydrogen bonds for a specific target showing the interrelation between long-range hydrogen bonds and hydrophobic interactions.
Figure 2.
Sequence and structural alignment of c-Src and c-Abl kinase.
(A) The sequence and secondary structure alignment of c-Src and c-Abl; sequence alignment of c-Src and c-Abl has been carried out using ClustalW. The secondary structure assigned with the SSEA server is depicted as orange cylindrical (alpha helices) and light-blue arrows (beta-strand). (B) Three-dimensional structural alignments of c-Src and c-Abl kinases; superimposed structure of c-Src (PDB ID 2H8H) and c-Abl (PDB ID 2FO0); color coding for the ribbon diagram of c-Src is sand yellow and for c-Abl is split-pea-green color. This figure was made using PyMOL program (www.pymol.org).
Figure 3.
Ligand-associated amino acids of c-Src and c-Abl Kinase.
(A) A stick model of active inhibitors 1, 12, 19 and 28 docked in c-Src with conserved hydrophobic amino acids is shown. (B) Stick model of active inhibitors 1, 12, 19 and 28 docked in c-Abl with conserved hydrophobic amino acids is shown. (C) Alignment of hydrophobic amino acids observed at the interface of c-Src (PDB ID 1Y57), c-Abl (PDB ID 1M52) and functionally important inhibitors as listed in Table S1: (1, 12, 19 and 28). In figure (B) and (C), structure was aligned using COOT [43] and figure was made by PyMOL program.
Figure 4.
Correlation between crystallographically determined and computationally- generated modeled structure.
(A) Heavy atom was docked between the ligand and hydrophobic amino acid in c-Src. (B) The sulfate group was at the interface of the ligand and hydrophobic amino acid. (C) Superimposed of (A) and (B) structure. All three figures were made by PyMOL program.
Table 1.
Summary of MFA results.
Figure 5.
Hydrophobic interactions and hydrogen bonding between ligands and target.
(A) Two-dimensional representations of interactions observed between c-Src and ligands listed in Table S1: (1, 12, 19 and 28). (B) Two-dimensional representations of interactions observed between c-Abl and ligands listed in Table S1: (1, 12, 19 and 28). Hydrogen bonds are depicted with dashed line and hydrophobic interactions are shown as arcs. Both the figures were made using LIGPLOT program.