Università degli studi di Modena e Reggio Emilia

Structure graphs, in which interacting amino acids/nucleotides correspond to linked nodes, represent cutting-edge tools to investigate macromolecular function. The graph-based approach defined as Protein Structure Network (PSN) was initially implemented in the Wordom software and subsequently in the webPSN server. PSNs are computed either on a molecular dynamics (MD) trajectory (PSN-MD) or on a single structure. In the latter case, information on atomic fluctuations is inferred from the Elastic Network Model-Normal Mode Analysis (ENM-NMA) (PSN-ENM). While Wordom performs both PSN-ENM and PSN-MD analyses but without output post-processing, the webPSN server performs only single-structure PSN-EMN but assisting the user in input setup and output analysis. Here we release for the first time the standalone software PSNtools, which allows calculation and post-processing of PSN analyses carried out either on single structures or on conformational ensembles. Relevant unique and novel features of PSNtools are either comparisons of two networks or computations of consensus networks on sets of homologous/analogous macromolecular structures or conformational ensembles. Network comparisons and consensus serve to infer differences in functionally different states of the same system or network-based signatures in groups of bio-macromolecules sharing either the same functionality or the same fold. In addition to the new software, here we release also an updated version of the webPSN server, which allows performing an interactive graphical analysis of PSN-MD, following the upload of the PSNtools output. PSNtools, the auxiliary binary version of Wordom software, and the WebPSN server are freely available at http://webpsn.hpc.unimo.it/wpsn3.php.

A mixed Protein Structure Network (PSN) and Elastic Network Model-Normal Mode Analysis (ENM-NMA)-based strategy (i.e. PSN-ENM) was developed to investigate structural communication in bio-macromolecules. Protein Structure Graphs (PSGs) are computed on a single structure, whereas information on system dynamics is supplied by ENM-NMA. The approach was implemented in a webserver (webPSN), which was significantly updated herein. The webserver now handles both proteins and nucleic acids and relies on an internal upgradable database of network parameters for ions and small molecules in all PDB structures. Apart from the radical restyle of the server and some changes in the calculation setup, other major novelties concern the possibility to: a) compute the differences in nodes, links, and communication pathways between two structures (i.e. network difference) and b) infer links, hubs, communities, and metapaths from consensus networks computed on a number of structures. These new features are useful to identify commonalties and differences between two different functional states of the same system or structural-communication signatures in homologous or analogous systems. The output analysis relies on 3D-representations, interactive tables and graphs, also available for download. Speed and accuracy make this server suitable to comparatively investigate structural communication in large sets of bio-macromolecular systems. URL: http://webpsn.hpc.unimore.it.