Automated Docking of Ligands to Antibodies: Methods and Applications

Sotriffer, Christoph A.; Flader, Wolfgang; Winger, Rudolf H.; Rode, Bernd M.; Liedl, Klaus R.; Várga, J.

doi:10.1006/meth.1999.0922

Cited by 76 publications

(53 citation statements)

References 98 publications

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“…General aspects of the docking of ligands into antibodies have been summarized recently in an excellent review (Sotriffer et al, 2000). Most published examples have been limited to testing of specific docking programs/protocols for their abilities to reproduce experimentally determined structures of ligand-protein complexes (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Although, algorithms have been proposed to deal with this challenge (e.g. Friedman et al, 1994;Apostolakis et al, 1998), the strategies, based on treating the host protein as a rigid molecule, have proved quite successful, for predicting binding modes of ligands, in docking procedures similar to the ones used in our work (Friedman et al, 1994;Sotriffer et al, 2000). Excluding the flexibility of the antibody combining site is a common practice in docking studies (Bohm and Klebe, 1996;Gschwend et al, 1996;Sotriffer et al, 2000).…”

Section: Approximations Involved In Using the Dock Programmentioning

confidence: 97%

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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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Section: Discussionmentioning

confidence: 99%

Section: Approximations Involved In Using the Dock Programmentioning

confidence: 97%

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

Yuriev¹,

Ramsland²,

Edmundson³

2001

J of Molecular Recognition

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“…To this end molecular modeling studies were carried out using the crystal structure of the LytA ChBD to find small molecules that could block the interaction of this domain with the cell wall of pneumococcus. The program AutoDock 3.0 (25) has been successfully used to predict HIV-1 protease inhibitor binding (31) and the binding of haptens to antibodies (32). Thus, we used this software to analyze the docking process.…”

Section: Docking Of Small M R Compounds Into the Chbss-mentioning

confidence: 99%

Ofloxacin-like Antibiotics Inhibit Pneumococcal Cell Wall-degrading Virulence Factors

Fernández‐Tornero

Garcı́a

Pascual‐Teresa

et al. 2005

Journal of Biological Chemistry

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The search for new drugs against Streptococcus pneumoniae (pneumococcus) is driven by the 1.5 million deaths it causes annually. Choline-binding proteins attach to the pneumococcal cell wall through domains that recognize choline moieties, and their involvement in pneumococcal virulence makes them potential targets for drug development. We have defined chemical criteria involved in the docking of small molecules from a three-dimensional structural library to the major pneumococcal autolysin (LytA) choline binding domain. These criteria were used to identify compounds that could interfere with the attachment of this protein to the cell wall, and several quinolones that fit this framework were found to inhibit the cell wall-degrading activity of LytA. Furthermore, these compounds produced similar effects on other enzymes with different catalytic activities but that contained a similar choline binding domain; that is, autolysin (LytC) and the phage lytic enzyme (Cpl-1). Finally, we resolved the crystal structure of the complex between the choline binding domain of LytA and ofloxacin at a resolution of 2.6 Å. These data constitute an important launch pad from which effective drugs to combat pneumococcal infections can be developed.

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“…Exceptions to this are the number of conformation results from a single molecular docking (100) and the amount of energy used to run the docking process evaluated using a LGA docking algorithm [3,4]. Each conformation generated was grouped into clusters based on the value of the RMSD, with a maximum tolerance RMSD value of each member in the cluster being 2 Å.…”

Section: Discussionmentioning

confidence: 99%

In Silico Binding Interaction Study of Mefenamic Acid and Piroxicam on Human Albumin

2017

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Objective: A drug can replace other drugs in the same binding position in protein plasma, increasing pharmacological response due to the increased free drug concentration. Drug shifting is critical when a compound is tightly bound to a protein. For example, a binding fraction change, from 98% to 94%, may increase the free fraction 3 times, from 2% to 6%. Knowing that there is an interaction between mefenamic acid and piroxicam on plasma protein, more specifically on human albumin, this study aimed to visualize the interaction between both drugs and human albumin in silico.Methods: This study used AutoDock4 as a molecular docking technique, obtaining binding visualizations, binding energies (ΔG), and inhibition constants (K i ) of both mefenamic acid-albumin and piroxicam-albumin bindings.Results: It is shown that the ΔG and K i of both mefenamic acid and piroxicam are −5.47 kcal/mol (98.59 µM) and −7.46 kcal/mol (3.42 µM), respectively. Conclusions:The process of binding mefenamic acid to albumin can be substituted with piroxicam due to its higher ΔG and K i values. It can be predicted that this interaction will increase the free mefenamic acid concentration in blood plasma which, in turn, enhances the therapeutic effect.

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Automated Docking of Ligands to Antibodies: Methods and Applications

Cited by 76 publications

References 98 publications

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

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

Ofloxacin-like Antibiotics Inhibit Pneumococcal Cell Wall-degrading Virulence Factors

In Silico Binding Interaction Study of Mefenamic Acid and Piroxicam on Human Albumin

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