Multiscale modelling of protein-protein interactions

The area of protein-protein interactions (PPI) is always exciting as proteins can be either monogamous or promiscuous with their interaction partners. Also, a hot topic these days in computational biology is multiscale modelling. It refers to the method of analyzing a system from atomistic and at a global scale and other scales, in between. Few years ago, a new method of co-evolutionary analysis of residues made news and has been used for gaining insights in other systems. Read the blog by Bosco Ho about the groundbreaking work here about Direct Coupling Analysis (DCA).


Example of a protein-protein interaction. By Dcrjsr – Own work, CC BY 3.0,

So, when two orthogonal approaches are used to understand a PPI system, it obviously becomes an interesting work. A recent paper in eLife reports exactly that. Malinverni et al report the use of coarse-grained simulation coupled with atomistic molecular dynamics simulation and data from DCA to identify the evolutionarily conserved residues that cause the specific interaction between Hsp70 and Hsp40.

ResearchBlogging.orgAs these two proteins are part of the chaperone machinery, any insight on the Hsp70’s ability to bind to proteins along with Hsp40 is crucial to understand the short-lived interaction. As mentioned in the article, vast amount of data (in terms of NMR, mutagenesis, etc.) is present that can be incorporated in this multiscale modelling.

The impact of the predicted interaction model is not only statistically significant, but also correlates well with the known experimental data.

Malinverni D, Jost Lopez A, De Los Rios P, Hummer G, Barducci A: Modeling Hsp70/Hsp40 interaction by multi-scale molecular simulations and coevolutionary sequence analysis. eLife 2017, 6. DOI:


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