Mutual synergistic folding (MSF) proteins belong to a recently emerged subclass of
disordered proteins, which are disordered in their monomeric forms but become ordered
in their oligomeric forms. They can be identified by experimental methods following
their unfolding, which happens in a single-step cooperative process, without the presence
of stable monomeric intermediates. Only a limited number of experimentally validated
MSF proteins are accessible. The amino acid composition of MSF proteins shows high
similarity to globular ordered proteins, rather than to disordered ones. However,
they have some special structural features, which makes it possible to distinguish
them from globular proteins. Even in the possession of their oligomeric three-dimensional
structure, classification can only be performed based on unfolding experiments, which
are frequently absent. In this work, we demonstrate a simple protocol using molecular
dynamics simulations, which is able to indicate that a protein structure belongs to
the MSF subclass. The presumption of the known atomic resolution quaternary structure
is an obvious limitation of the method, and because of its high computational time
requirements, it is not suitable for screening large databases; still, it is a valuable
in silico tool for identification of MSF proteins.
