Robotic-inspired approach to multi-domain membrane receptor conformation space: theory and SARS-CoV-2 spike protein case study

  • The spike protein of SARS-CoV-2 is a highly flexible membrane receptor that triggers the translocation of the virus into cells by attaching to the human receptors. Like other type I membrane receptors, this protein has several extracellular domains connected by flexible hinges. The presence of these hinges results in high flexibility, which consequently results in challenges in defining the conformation of the protein. Here, We developed a new method to define the conformational space based on a few variables inspired by the robotic field’s methods to determine a robotic arm’s forward kinematics. Using newly performed atomistic molecular dynamics (MD) simulations and publicly available data, we found that the Denavit-Hartenberg (DH) parameters can reliably show the changes in the local conformation. Furthermore, the rotational and translational components of the homogenous transformation matrix constructed based on the DH parameters can identify the changes in the global conformation of the spike and also differentiate between the conformation with a similar position of the spike head, which other types of parameters, such as spherical coordinates, fail to distinguish between such conformations. Finally, the new method will be beneficial for looking at the conformational heterogeneity in all other type I membrane receptors.

Download full text files

Export metadata

Metadaten
Author:Alen T. MathewORCiD, Mateusz SikoraORCiD, Gerhard HummerORCiD, Ahmad Reza MehdipourORCiDGND
URN:urn:nbn:de:hebis:30:3-835948
URL:https://www.biorxiv.org/content/10.1101/2024.03.29.587391v1
DOI:https://doi.org/10.1101/2024.03.29.587391
Parent Title (English):bioRxiv
Publisher:bioRxiv
Document Type:Preprint
Language:English
Date of Publication (online):2024/04/01
Date of first Publication:2024/04/01
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/04/16
Issue:2024.03.29.587391 Version 1
Edition:Version 1
Page Number:24
HeBIS-PPN:518161188
Institutes:Physik
Angeschlossene und kooperierende Institutionen / MPI für Biophysik
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International