Concordia University

CHEM 375

Introduction The objective of this experiment was to observe and record the differences in proteinligand binding interactions between human dihydrofolate reductase bound with folate ligand (1DHF) and human dihydrofolate reductase bound with 5-deazafolate ligand (2DHF). This was determined by observing the effect of replacing the nitrogen with a carbon at position 5 in the ligands in 2DHF which was predicted to decrease the polarity of position 5 and to increase the polarity of the nitrogen at position 8 in the ligand. Binding interactions could be van der Waals interactions, electrostatic forces or hydrogen bonds. Any changes in the structure of the protein or the ligand, such as the replacement of a nitrogen with a carbon, will have an effect on the strength of these binding interactions. In turn, that strength is influenced by the proximity of the groups involved. Data and Results Table 1. Description of the Dihydrofolate Reductase with Folate Bound (1DHF) and the with 5- Deazafolate bound (2DHF) to compare their binding interactions. 1DHF 2DHF Secondary Structure 4 α -helices and 9 β -strands 4 α -helices and 9 β -strands Ligand description Hydrophobic parts are within the ligand and hydrophilic parts are exposed. Hydrophobic parts are within the ligand and hydrophilic parts are exposed. Number of atoms within 5 Å distance of the ligand 249 atoms 257 atoms Ligand-protein interaction Hydrophobic parts experience van der Waals interactions while hydrophilic parts experience dipoledipole interactions. Hydrophobic parts experience van der Waals interactions while hydrophilic parts experience dipole-dipole interactions. Table 2. Identifying Amino Acids in 1DHF closest to the Ligand to compare the distance with those of 2DHF and to determine differences in interaction. N-5 position N-8 position Closest A.A. or Molecule Distance (Å) Type of Interactions Closest A.A. or Molecule Distance (Å) Type of Interactions Leu 22 4.93 van der Waals Ile 7 3.87 van der Waals Phe 31 4.84 van der Waals H2O 406 3.98 van der Waals Phe 34 4.85 van der Waals Val 8 3.70 van der Waals H2O 406 3.90 van der Waals Tyr 121 3.52 H-bond