PRO-Simat: Protein network simulation and design tool

Rana Salihoglu; Mugdha Srivastava; Chunguang Liang; Klaus Schilling; Aladar Szalay; Elena Bencurova; Thomas Dandekar

doi:10.1016/j.csbj.2023.04.023

PRO-Simat: Protein network simulation and design tool

Comput Struct Biotechnol J. 2023 Apr 26:21:2767-2779. doi: 10.1016/j.csbj.2023.04.023. eCollection 2023.

Authors

Rana Salihoglu¹, Mugdha Srivastava^{1

2}, Chunguang Liang¹, Klaus Schilling³, Aladar Szalay^{4

5

6}, Elena Bencurova¹, Thomas Dandekar^{1

7}

Affiliations

¹ Department of Bioinformatics, University of Würzburg, Würzburg, Germany.
² Core Unit Systems Medicine, University of Würzburg, 97080 Würzburg, Germany.
³ Informatics VII, Robotics and Telematics, Department of Mathematics and Informatics, Am Hubland, University of Würzburg, D-97074 Würzburg, Germany.
⁴ Dept. of Biochemistry, Biocenter, Am Hubland, University of Würzburg, D-97074 Würzburg, Germany.
⁵ Department of Radiation Medicine and Applied Sciences, Rebecca & John Moores Comprehensive Cancer Center, University of California, San Diego, CA, USA.
⁶ Dept. of Pathology, Center of Immune technologies, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁷ Structural and Computational Biology, European Molecular Biology Laboratory, Heidelberg, Germany.

Abstract

PRO-Simat is a simulation tool for analysing protein interaction networks, their dynamic change and pathway engineering. It provides GO enrichment, KEGG pathway analyses, and network visualisation from an integrated database of more than 8 million protein-protein interactions across 32 model organisms and the human proteome. We integrated dynamical network simulation using the Jimena framework, which quickly and efficiently simulates Boolean genetic regulatory networks. It enables simulation outputs with in-depth analysis of the type, strength, duration and pathway of the protein interactions on the website. Furthermore, the user can efficiently edit and analyse the effect of network modifications and engineering experiments. In case studies, applications of PRO-Simat are demonstrated: (i) understanding mutually exclusive differentiation pathways in Bacillus subtilis, (ii) making Vaccinia virus oncolytic by switching on its viral replication mainly in cancer cells and triggering cancer cell apoptosis and (iii) optogenetic control of nucleotide processing protein networks to operate DNA storage. Multilevel communication between components is critical for efficient network switching, as demonstrated by a general census on prokaryotic and eukaryotic networks and comparing design with synthetic networks using PRO-Simat. The tool is available at https://prosimat.heinzelab.de/ as a web-based query server.

Keywords: Network simulation; Protein analysis; Signalling pathways, dynamic protein-protein interactions, optogenetics, oncolytic virus, DNA storage.