Insight into odorant perception: the crystal structure and binding characteristics of antibody fragments directed against the musk odorant traseolide

Langedijk, Annette C; Spinelli, S.; Anguille, Christelle; Hermans, Pim; Nederlof, J.; Butenandt, Jens; Honegger, Annemarie; Cambillau, Christian; Plückthun, Andreas

doi:10.1006/jmbi.1999.3101

Cited by 8 publications

(5 citation statements)

References 75 publications

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“…Structure 1c12 is a complex of traseolide, which is a musk odorant, with an antibody directed against it (only the Fab portion of the antibody was crystallized) . Docking in the absence of water molecules (NoW) correctly reproduced the native binding mode: the RMSD of the top-ranked solution was 1.06 Å, with respect to the crystallographic binding mode.…”

Section: Resultsmentioning

confidence: 99%

Ligand−Protein Docking with Water Molecules

Roberts

Mancera

2008

J. Chem. Inf. Model.

135

116

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The presence of water molecules plays an important role in the accuracy of ligand-protein docking predictions. Comprehensive docking simulations have been performed on a large set of ligand-protein complexes whose crystal structures contain water molecules in their binding sites. Only those water molecules found in the immediate vicinity of both the ligand and the protein were considered. We have investigated whether prior optimization of the orientation of water molecules in either the presence or absence of the bound ligand has any effect on the accuracy of docking predictions. We have observed a statistically significant overall increase in accuracy when water molecules are included during docking simulations and have found this to be independent of the method of optimization of the orientation of water molecules. These results confirm the importance of including water molecules whenever possible in a ligand-protein docking simulation. Our findings also reveal that prior optimization of the orientation of water molecules, in the absence of any bound ligand, does not have a detrimental effect on the improved accuracy of ligand-protein docking. This is important, given the use of docking simulations to predict the binding modes of new ligands or drug molecules.

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Section: Resultsmentioning

confidence: 99%

Ligand−Protein Docking with Water Molecules

Roberts

Mancera

2008

J. Chem. Inf. Model.

135

116

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“…Hydrophobicity maps were calculated and displayed also for the following complexes: leucine zipper (PDB code 2zta), 52,53 progesterone and DB3 antibody Fv (1dbb), 54 traseolide and M02/05/01 antibody Fab, 55 hirustasin and kallikrein (1hia), 56 acetyl-pepstatin and HIV1 protease (5hvp). 57 In all cases, the regions where the nonpolar parts of the ligands bind are correctly predicted by the hydrophobicity maps.…”

Section: Other Complexesmentioning

confidence: 99%

Hydrophobicity at the surface of proteins

Scarsi¹,

Majeux²,

Caflisch³

1999

Proteins

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A new method is presented to quantitatively estimate and graphically display the propensity of nonpolar groups to bind at the surface of proteins. It is based on the calculation of the binding energy, i.e., van der Waals interaction plus protein electrostatic desolvation, of a nonpolar probe sphere rolled over the protein surface, and on the color coding of this quantity on a smooth molecular surface (hydrophobicity map). The method is validated on ten protein-ligand complexes and is shown to distinguish precisely where polar and nonpolar groups preferentially bind. Comparisons with existing approaches, like the display of the electrostatic potential or the curvature, illustrate the advantages and the better predictive power of the present method. Hydrophobicity maps will play an important role in the characterization of binding sites for the large number of proteins emerging from the genome projects and structure modeling approaches. Proteins 1999;37:565-575. 1999 Wiley-Liss, Inc.

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“…Interestingly, the binding of a ligand (e.g., testosterone, steroids, musk odorant) to a deep hydrophobic pocket in a Fab is often hypothesized to be regulated by shape complementarity and the concomitant desolvation of the complementary surfaces with a subsequent rise in system entropy. 58 In the case of the fentanyl-specific antibodies described here, the entropy change was unfavorable, indicating that conformational rearrangements of Fab loops were likely required to form the pocket around fentanyl. Unbound Fab should exhibit higher degrees of freedom, which are lost upon ligand binding, leading to an entropy drop.…”

Section: Resultsmentioning

confidence: 84%