PocketOptimizer 2.0 : A modular framework for computer‐aided ligand‐binding design

Title data

Noske, Jakob ; Kynast, Josef ; Lemm, Dominik ; Schmidt, Steffen ; Höcker, Birte:
PocketOptimizer 2.0 : A modular framework for computer‐aided ligand‐binding design.
In: Protein Science. Vol. 32 (2023) Issue 1 . - e4516.
ISSN 1469-896X
DOI: https://doi.org/10.1002/pro.4516

Official URL:

Abstract in another language

The ability to design customized proteins to perform specific tasks is of great interest. We are particularly interested in the design of sensitive and specific small molecule ligand-binding proteins for biotechnological or biomedical applications. Computational methods can narrow down the immense combinatorial space to find the best solution, and thus provide starting points for experimental procedures. However, success rates strongly depend on accurate modelling and energetic evaluation. Not only intra- but also intermolecular interactions have to be considered. To address this problem, we developed PocketOptimizer, a modular computational protein design pipeline, that predicts mutations in the binding pockets of proteins to increase affinity for a specific ligand. Its modularity enables users to compare different combinations of force fields, rotamer libraries, and scoring functions. Here we present a much-improved version - PocketOptimizer 2.0. We implemented a cleaner user interface, an extended architecture with more supported tools such as force fields and scoring functions, a backbone-dependent rotamer library, as well as different improvements in the underlying algorithms. Version 2.0 was tested against a benchmark of design cases and assessed in comparison to the first version. Our results show how the newly implemented features such as the new rotamer library can lead to improved prediction accuracy. Therefore, we believe that PocketOptimizer 2.0 with its many new and improved functionalities provides a robust and versatile environment for the design of small molecule binding pockets in proteins. It is widely applicable and extendible due to its modular framework. PocketOptimizer 2.0 can be downloaded at https://github.com/Hoecker-Lab/pocketoptimizer. This article is protected by copyright. All rights reserved.

Further data

Item Type:	Article in a journal
Refereed:	Yes
Institutions of the University:	Faculties Faculties > Faculty of Biology, Chemistry and Earth Sciences Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry > Chair Biochemistry - Univ.-Prof. Dr. Birte Höcker Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Professorship Biochemistry
Result of work at the UBT:	Yes
DDC Subjects:	500 Science 500 Science > 500 Natural sciences 500 Science > 540 Chemistry 500 Science > 570 Life sciences, biology
Date Deposited:	09 Dec 2022 06:39
Last Modified:	23 Aug 2023 13:27
URI:	https://eref.uni-bayreuth.de/id/eprint/72981