The current abundance of genetic variant data requires new tools to develop mechanistic hypotheses about biological processes and diseases. Fortunately, growing datasets of protein interactions, mechanism and structure can provide help understand or predict biological mechanism. However, a systematic integration of these datasets is first needed. For this purpose, we developed Mechnetor.

For sets of proteins or interactions, the tool integrates mechanistic data from diverse sources (below) and constructs an interactive network for intuitive visualization of interaction mechanisms. Proteins are represented as linear arrangements of domains, motifs and other functional elements, which permits the display of interactions between the relevant/known protein regions. The result is a finer resolution interaction network and more immediate clues as to points of intervention. The view can be customized and manipulated, and exported as an image or vector graphics (SVG) at any time, providing beautiful figures suitable for publication.

Mechnetor is free and open to all users and there is no login requirement.

For more details, check out:

Mechnetor: a web server for exploring protein mechanism and the functional context of genetic variants
González-Sánchez J.C., Ibrahim M.F.R., Leist I.C., Weise K.R. and Russell R.B
Nucleic Acid Research, Jul 2;49(W1):W366-W374 (2021)

Mechnetor requires protein pairs so that it can look for interactions between them. Users can provide their input in different ways but always using gene names, UniProt accessions or UniProt identifiers.

You can input a list of proteins (one protein per line) and it will look for interactions between every possible protein pair. If you want to restric it to particular pairs, then enter a list of protein pairs (two proteins in the same line space-separated).
Using the slider below, you can automatically add a number of known interactors per each protein. These are always retrieved in order of the amount of evidence according to the PPI database. This option makes possible simple queries of a single protein and few of its most common interactors.

You can input any number of protein mutations or modifications (always one per line), following the specified format. Mutations will be mapped to their corresponding positions within the protein but they are not neccessary to run a job. At the same time, any protein in the mutation input box will be added to the network, thus it's not neccessary to enter it on both boxes.

Mechnetor creates a mechanistic network with the proteins and variants you provided, with proteins and their different functional elements arranged linearly, and variants displayed on them. This network is highly interactive and the user is encouraged to manually explore their results using the mouse controls and several toggle buttons and sliders (see the Quick Guide). The initial protein positions within the network are arbitrary. You can drag them around as it suits you better.

The current network view can be exported as an image (JPG, PNG) or vector graphics (SVG) at any time.

The different interaction evidence displayed in the network (domain-domain interactions, domain-motif interactions, interacting regions from annotation, predicted interaction interfaces) is also contained in a browsable list, that can also be downloaded in different formats.

The results page can be bookmarked and accessed later. Results will be kept for at least 6 months.

This are all the data sources currently used by Mechnetor:

Database	Version/Release
UniProt	2020_05
Pfam	33.1
ELM	March 2020
3did	2020-01
BioGRID	4.2.191
PhosphoSitePlus	March 2019
COSMIC	v87

It also runs InterPreTS, our tool to predict interactions through tertiary structure.

Currently, it supports human and 6 other model organisms.