Item type:Thesis, Open Access

Methods for the Efficient Comparison of Protein Binding Sites and for the Assessment of Protein-Ligand Complexes

Thumbnail Image

Files

dtk.pdf (10.52 MB)

Date

2015-09-10

Authors

Publisher

Philipps-Universität Marburg
DOI

Supervisors

Abstract

In the present work, accelerated methods for the comparison of protein binding sites as well as an extended procedure for the assessment of ligand poses in protein binding sites are presented. Protein binding site comparisons are frequently used receptor-based techniques in early stages of the drug development process. Binding sites of other proteins which are similar to the binding site of the target protein can offer hints for possible side effects of a new drug prior to clinical studies. Moreover, binding site comparisons are used as an idea generator for bioisosteric replacements of individual functional groups of the newly developed drug and to unravel the function of hitherto orphan proteins. The structural comparison of binding sites is especially useful when applied on distantly related proteins as a comparison solely based on the amino acid sequence is not sufficient in such cases. Methods for the assessment of ligand poses in protein binding sites are also used in the early phase of drug development within docking programs. These programs are utilized to screen entire libraries of molecules for a possible ligand of a binding site and to furthermore estimate in which conformation the ligand will most likely bind. By employing this information, molecule libraries can be filtered for subsequent affinity assays and molecular structures can be refined with regard to affinity and selectivity.

Review

Metadata

Contributors
Supervisor:
Dates
Created: 2015Issued: 2015-09-10
DOI
https://doi.org/10.17192/z2015.0384
Faculty
Fachbereich Pharmazie
Publisher
Philipps-Universität Marburg
Language
eng
Data types
DoctoralThesis
Keywords
CavbaseKlassifizierungClassificationCavbase
DFG-subjects
GraphBindestelleProteineHistogrammWirkstoffClique
DDC-Numbers
610
License
https://rightsstatements.org/vocab/InC-NC/1.0/
URI
https://open.uni-marburg.de/handle/10.17192/z2015.0384
show more
Krotzky, Timo (1076292879): Methods for the Efficient Comparison of Protein Binding Sites and for the Assessment of Protein-Ligand Complexes. : Philipps-Universität Marburg 2015-09-10. DOI: https://doi.org/10.17192/z2015.0384.

License

item.page.license.under-copyright
This item has been published with the following license: In Copyright