Disputation von Nils-Ole Friedrich am 27.10.2020, 15:00 Uhr

27. Oktober 2020, von Reinhard Zierke

Einladung zur hochschulöffentlichen Disputation von
Herrn Nils-Ole Friedrich

Titel der Dissertation:
Development and Validation of Algorithms for the Generation of Conformer Ensembles Representing Protein-Bound Ligand Conformations

Abstract:
Many applications in computational drug discovery rely on conformational ensembles to adequately represent the flexibility of small molecules in 3D space. The generation of conformational ensembles is a complex problem because of the high number of degrees of freedom, even for small molecules.

In this thesis, a fully automated cheminformatics pipeline for the selection and extraction of high-quality protein-bound ligand conformations from X-ray structural data was developed. The resulting datasets were of adequately high quality and sufficient size for thorough benchmark studies of conformer ensemble generators, which allow statements on the statistical significance of differences in performance between algorithms. The datasets were utilized to conduct the most comprehensive benchmark study of conformer ensemble generators to date, comparing the performance of seven freely available and eight commercial algorithms.

The findings and experience gained during the benchmarking studies and the analysis of the variability of bioactive conformations was used for the development of Conformator, a new knowledge-based algorithm for generating conformer ensembles. The conformer ensembles generated by Conformator are significantly more accurate than those of all free tools tested, and there is no significant difference to the best performing commercial algorithm. Conformator, with its high accuracy and speed, as well as its robustness with respect to input formats, molecular geometries, and its handling of macrocycles, effectively closes the gap between commercial and freely available algorithms.

Datum und Uhrzeit: Dienstag, 27. Oktober 2020 um 15:00 Uhr
Ort: per Videokonferenz in Zoom
Betreuer: Prof. Dr. Johannes Kirchmair

Bei Interesse an der Videokonferenz teilzunehmen, melden Sie sich bitte bei Nils-Ole Friedrich(friedrich"AT"zbh.uni-hamburg.de).

Prof. Dr. Matthias Rarey
Vorsitzender des Fach-Promotionsausschusses Informatik