Rinmaker: a fast, versatile and reliable tool to determine residue interaction networks in proteins

Abstract

Background: Residue Interaction Networks (RINs) map the crystallographic description of a protein into a graph, where amino acids are represented as nodes and non-covalent bonds as edges. Determination and visualization of a protein as a RIN provides insights on the topological properties (and hence their related biological functions) of large proteins without dealing with the full complexity of the three-dimensional description, and hence it represents an invaluable tool of modern bioinformatics.

Results: We present RINmaker, a fast, flexible, and powerful tool for determining and visualizing RINs that include all standard non-covalent interactions. RINmaker is offered as a cross-platform and open source software that can be used either as a command-line tool or through a web application or a web API service. We benchmark its efficiency against the main alternatives and provide explicit tests to show its performance and its correctness.

Conclusions: RINmaker is designed to be fully customizable, from a simple and handy support for experimental research to a sophisticated computational tool that can be embedded into a large computational pipeline. Hence, it paves the way to bridge the gap between data-driven/machine learning approaches and numerical simulations of simple, physically motivated, models.

Keywords: Non-covalent bonds; Protein 3D structure; Residue interaction network (RIN).

Fig. 1

The RINmaker flow: The 3D structure of a protein (left) is mapped into a RIN network (right) via different possibilities (command-line, web API and web GUI). As a specific example, the red and blue amino acids highlighted in the protein structure on the left are mapped into the corresponding nodes on the right

Fig. 2

The RINmaker user interface: RIN 3D visualization

Fig. 3

Native state of the Trp-Cage miniprotein with a $C{l}^{-}$ as counter ion (Model 1 in the 1L2Y.pdb file)

Fig. 4

Betweenness centrality of the Trp-Cage residues as a function of the simulation time $t/\mathrm{\Delta }t$ ($\mathrm{\Delta }t=30$ psec) during the trajectory at temperatures above and below the folding temperature ($\approx 400K$). Top panel $T=330K$; Bottom panel $T=480K$

Fig. 5

Free energy landscape of Trp-Cage as a function of the radius of gyration and of the betweenness centrality at temperatures (left) T = 330 K and (right) T = 480 K. Snapshots of the conformation corresponding to stable local minima are given in A for T = 330 K and in B for T = 480 K with highlighted the Gly11, Arg16 and Tpr6 residues involved in the transition between one minimum to the other. In B it is also possible to observe the denaturated $\alpha$-helix highlighted in yellow

Fig. 6

Betweenness centrality of residue Trp6 in the Trp-Cage trajectory obtained from RINmaker, at the two different temperatures (T = 330 K and T = 480 K)

Fig. 7

Performance tests: CPU time as a function of the number of residues. RINmaker (blue) vs. RING 3.0 (orange)