Version 1
: Received: 25 February 2024 / Approved: 26 February 2024 / Online: 27 February 2024 (13:29:47 CET)
How to cite:
Li, W. High-Throughput Extraction of Interfacial Electrostatic Features from GLP-1-GLP-1R Complex Structures: A GLP-1-GLP-1R-Based Mini GIBAC Perspective. Preprints2024, 2024021519. https://doi.org/10.20944/preprints202402.1519.v1
Li, W. High-Throughput Extraction of Interfacial Electrostatic Features from GLP-1-GLP-1R Complex Structures: A GLP-1-GLP-1R-Based Mini GIBAC Perspective. Preprints 2024, 2024021519. https://doi.org/10.20944/preprints202402.1519.v1
Li, W. High-Throughput Extraction of Interfacial Electrostatic Features from GLP-1-GLP-1R Complex Structures: A GLP-1-GLP-1R-Based Mini GIBAC Perspective. Preprints2024, 2024021519. https://doi.org/10.20944/preprints202402.1519.v1
APA Style
Li, W. (2024). High-Throughput Extraction of Interfacial Electrostatic Features from GLP-1-GLP-1R Complex Structures: A GLP-1-GLP-1R-Based Mini GIBAC Perspective. Preprints. https://doi.org/10.20944/preprints202402.1519.v1
Chicago/Turabian Style
Li, W. 2024 "High-Throughput Extraction of Interfacial Electrostatic Features from GLP-1-GLP-1R Complex Structures: A GLP-1-GLP-1R-Based Mini GIBAC Perspective" Preprints. https://doi.org/10.20944/preprints202402.1519.v1
Abstract
From a structural point of view, understanding interfacial electrostatic features of ligand-receptor complexes is crucial for biophysics-based design of therapeutics with improved efficacy and safety. Here, with a high-throughput structural feature extraction approach, this article reports a set of electrostatic structural features from glucagon-like peptide-1 (GLP-1) and GLP-1 receptor (GLP-1R) complex structures determined using experimental tools. Leveraging a set of computational structural biophysical analyses, this article systematically characterized the electrostatic interactions within the GLP-1-GLP-1R complexes with two sets of criteria to identify interfacial salt bridges and hydrogen bonds. Overall, the results here reveal intricate details of electrostatic interactions critical for GLP-1 binding to its receptor GLP-1R, providing biophysical insights into the stabilization of the GLP-1-GLP-1R complex structure and the molecular basis of GLP-1/GLP-1R signaling. Furthermore, the electrostatic structural features extracted from GLP-1 and GLP-1R complex structures are useful in the development of a machine learning-based ligand-receptor binding affinity calculating model, i.e., a GLP-1-GLP-1R-specific general intermolecular binding affinity calculator (GIBAC), paving the way for accelerated discovery and structure-based design of drug candidates targeting the GLP-1/GLP-1R system with improved efficacy and safety.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
