Ligand Binding by Antibody IgE Lb4: Assessment of Binding Site Preferences Using Microcalorimetry, Docking, and Free Energy Simulations

Sotriffer, Christoph A.; Flader, Wolfgang; Cooper, Alan; Rode, Bernd M.; Linthicum, D. Scott; Liedl, Klaus R.; Várga, J.

doi:10.1016/s0006-3495(99)77451-5

Cited by 12 publications

(8 citation statements)

References 57 publications

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“…Sotriffer et al (148) showed a good example of how theoretical work could be carried out without direct experimental data, and they were able to provide useful information for designing new ligands. Starting from an antibody structure obtained by homology modeling (37), Sotriffer et al performed extensive docking searches to identify two pockets, S1 and S2, in the antibody IgE LB4 as the most probable binding site for three dinitrophenyl (DNP) amino acids (DNPalanine, DNP-glycine, and DNP-serine).…”

Section: Free Energy Perturbation and Thermodynamic Integration Methodsmentioning

confidence: 99%

Biomolecular Simulations: Recent Developments in Force Fields, Simulations of Enzyme Catalysis, Protein-Ligand, Protein-Protein, and Protein-Nucleic Acid Noncovalent Interactions

Wang

Donini

Reyes

et al. 2001

Annu. Rev. Biophys. Biomol. Struct.

515

436

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Computer modeling has been developed and widely applied in studying molecules of biological interest. The force field is the cornerstone of computer simulations, and many force fields have been developed and successfully applied in these simulations. Two interesting areas are (a) studying enzyme catalytic mechanisms using a combination of quantum mechanics and molecular mechanics, and (b) studying macromolecular dynamics and interactions using molecular dynamics (MD) and free energy (FE) calculation methods. Enzyme catalysis involves forming and breaking of covalent bonds and requires the use of quantum mechanics. Noncovalent interactions appear ubiquitously in biology, but here we confine ourselves to review only noncovalent interactions between protein and protein, protein and ligand, and protein and nucleic acids.

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Section: Free Energy Perturbation and Thermodynamic Integration Methodsmentioning

confidence: 99%

Biomolecular Simulations: Recent Developments in Force Fields, Simulations of Enzyme Catalysis, Protein-Ligand, Protein-Protein, and Protein-Nucleic Acid Noncovalent Interactions

Wang

Donini

Reyes

et al. 2001

Annu. Rev. Biophys. Biomol. Struct.

515

436

View full text Add to dashboard Cite

show abstract

“…To overcome this shortcoming, biochemical data [e.g. binding constants (Sotriffer et al, 1999), critical mutations (Cherfils et al, 1994Stigler et al, 1999), NMR distance restraints (Scherf et al, 1992)] may be used to 'filter out' and/or rationalize the docking results. On the other hand, such outcomes may actually be viewed as advantages when alternative binding modes are of interest.…”

Section: Correlation Between Experimental Binding Data and Docking Rementioning

confidence: 99%

“…Moreover, docking yields separate energy scores for individual ligand configurations. In contrast, binding energy values generated by experimental approaches, such as isothermal titration calorimetry (Sleigh et al, 1999;Sotriffer et al, 1999), are averages weighted over a range of configurations. Thus, instead of a single Ab-ligand structure/binding energy value, this technique produces a composite map of the binding site complete with a pattern of potential contact points used by different ligands and ligand configurations.…”

Section: Introductionmentioning

confidence: 99%

Docking of combinatorial peptide libraries into a broadly cross‐reactive human IgM

Yuriev¹,

Ramsland²,

Edmundson³

2001

J of Molecular Recognition

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A monoclonal IgM cryoglobulin with diverse binding behavior was isolated from a patient (Mez) with Waldenström's macroglobulinemia. It gave very high titers in the binding of combinatorially synthesized libraries of peptides ranging in size from two to eight residues. The crystal structure of Mez Fv revealed that the binding site was divided into two cavities of unequal volumes with dimensions and chemical properties that were compatible with the binding of peptides. Access to this unique combination of structural information and peptide binding data led us to carry out Mez-peptide docking simulations to gain insight into the Mez binding propensities. In the present article, the results for docking of five peptide libraries are combined with discussions of the methods and approximations involved in the docking process. We analyze the origins of peptide binding affinity for Mez IgM in terms of its cross-reactivity and its structural preferences.

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“…In most published docking applications, only the third step is taken, and the binding modes of small ligands have been reproduced (Stigler et al 1999; Sotriffer et al 1999, 2000). In all these cases, the binding site was predetermined, and therefore, the search space was limited to that region of the protein in the docking simulations.…”

mentioning

confidence: 99%

Efficient docking of peptides to proteins without prior knowledge of the binding site

2002

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Reliability in docking of ligand molecules to proteins or other targets is an important challenge for molecular modeling. Applications of the docking technique include not only prediction of the binding mode of novel drugs, but also other problems like the study of protein-protein interactions. Here we present a study on the reliability of the results obtained with the popular AutoDock program. We have performed systematical studies to test the ability of AutoDock to reproduce eight different protein/ligand complexes for which the structure was known, without prior knowledge of the binding site. More specifically, we look at factors influencing the accuracy of the final structure, such as the number of torsional degrees of freedom in the ligand. We conclude that the Autodock program package is able to select the correct complexes based on the energy without prior knowledge of the binding site. We named this application blind docking, as the docking algorithm is not able to "see" the binding site but can still find it. The success of blind docking represents an important finding in the era of structural genomics.

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Ligand Binding by Antibody IgE Lb4: Assessment of Binding Site Preferences Using Microcalorimetry, Docking, and Free Energy Simulations

Cited by 12 publications

References 57 publications

Biomolecular Simulations: Recent Developments in Force Fields, Simulations of Enzyme Catalysis, Protein-Ligand, Protein-Protein, and Protein-Nucleic Acid Noncovalent Interactions

Biomolecular Simulations: Recent Developments in Force Fields, Simulations of Enzyme Catalysis, Protein-Ligand, Protein-Protein, and Protein-Nucleic Acid Noncovalent Interactions

Docking of combinatorial peptide libraries into a broadly cross‐reactive human IgM

Efficient docking of peptides to proteins without prior knowledge of the binding site

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