4I7J

T4 Lysozyme L99A/M102H with benzene bound

Summary for 4I7J

• Entry DOI: 10.2210/pdb4i7j/pdb
• Related: 4E97 4EKP 4EKQ 4EKR 4EKS
• Descriptor: Lysozyme, BETA-MERCAPTOETHANOL, BENZENE, ... (7 entities in total)
• Functional Keywords: hydrolase
• Biological source: Enterobacteria phage T4
• Total number of polymer chains: 2
• Total formula weight: 44264.66

Authors

Merski, M.,Shoichet, B.K. (deposition date: 2012-11-30, release date: 2013-03-27, Last modification date: 2023-09-20)

Primary citation

Merski, M.,Shoichet, B.K.
The impact of introducing a histidine into an apolar cavity site on docking and ligand recognition.
J.Med.Chem., 56:2874-2884, 2013

PubMed Abstract: Simplified model binding sites allow one to isolate entangled terms in molecular energy functions. Here, we investigate the effects on ligand recognition of the introduction of a histidine into a hydrophobic cavity in lysozyme. We docked 656040 molecules and tested 26 highly and nine poorly ranked. Twenty-one highly ranked molecules bound and five were false positives, while three poorly ranked molecules were false negatives. In the 16 X-ray complexes now known, the docking predictions overlaid well with the crystallographic results. Although ligand enrichment was high, the false negatives, the false positives, and the inability to rank order illuminated weaknesses in our scoring, particularly overweighed apolar and underweighted polar terms. Adjusting these led to new problems, reflecting the entangled nature of docking scoring functions. Changes in ligand affinity relative to other lysozyme cavities speak to the subtleties of molecular recognition even in these simple sites and to their relevance for testing different models of recognition.

PubMed: 23473072
DOI: 10.1021/jm301823g

Experimental method

X-RAY DIFFRACTION (1.67 Å)