TY - JOUR A1 - Salihoglu, Rana A1 - Srivastava, Mugdha A1 - Liang, Chunguang A1 - Schilling, Klaus A1 - Szalay, Aladar A1 - Bencurova, Elena A1 - Dandekar, Thomas T1 - PRO-Simat: Protein network simulation and design tool JF - Computational and Structural Biotechnology Journal N2 - 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. KW - network simulation KW - protein analysis KW - signalling pathways KW - dynamic protein-protein interactions KW - optogenetics KW - oncolytic virus KW - DNA storage Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350034 SN - 2001-0370 VL - 21 ER -