4i7r
T4 Lysozyme L99A/M102H with 2-(pyrazolo-1-yl) ethanol bound
Structural highlights
FunctionENLYS_BPT4 Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.[1] Publication Abstract from PubMedSimplified 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. The Impact of Introducing a Histidine into an Apolar Cavity Site on Docking and Ligand Recognition.,Merski M, Shoichet BK J Med Chem. 2013 Mar 20. PMID:23473072[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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