NAPS update: network analysis of molecular dynamics data and protein-nucleic acid complexes

Abstract

Network theory is now a method of choice to gain insights in understanding protein structure, folding and function. In combination with molecular dynamics (MD) simulations, it is an invaluable tool with widespread applications such as analyzing subtle conformational changes and flexibility regions in proteins, dynamic correlation analysis across distant regions for allosteric communications, in drug design to reveal alternative binding pockets for drugs, etc. Updated version of NAPS now facilitates network analysis of the complete repertoire of these biomolecules, i.e., proteins, protein-protein/nucleic acid complexes, MD trajectories, and RNA. Various options provided for analysis of MD trajectories include individual network construction and analysis of intermediate time-steps, comparative analysis of these networks, construction and analysis of average network of the ensemble of trajectories and dynamic cross-correlations. For protein-nucleic acid complexes, networks of the whole complex as well as that of the interface can be constructed and analyzed. For analysis of proteins, protein-protein complexes and MD trajectories, network construction based on inter-residue interaction energies with realistic edge-weights obtained from standard force fields is provided to capture the atomistic details. Updated version of NAPS also provides improved visualization features, interactive plots and bulk execution. URL: http://bioinf.iiit.ac.in/NAPS/.

Figure 1.

The NAPS workflow for the construction and analysis of protein, protein–protein/DNA/RNA complex, RNA and Molecular Dynamics trajectories. The network construction and analyses options available for the input types are marked by superscript numbers. New features introduced in updated NAPS are highlighted in ‘red’ colour and ‘*’ indicates that the option is available for all 6 input types.

Figure 2.

Network analysis of ubiquitin simulation. (A)–(D) show comparative analysis of two intermediate time-steps of the simulation. (A) 2D contact map showing common edges in ‘grey’ while edges specific to the time-steps 1 and 2 are shown in ‘blue’ and ‘green’ colours respectively. (B) 3D network view showing all nodes and common edges in the two time-steps in ‘grey’ while the edges specific to time-steps 1 and 2 are shown in ‘blue’ and ‘green’ colours respectively. (C) 3D molecular view using NGL showing the structures of the two time-steps in ‘blue’ and ‘green’ colours. (D) Overlap of the betweenness centrality plot for the two time-steps is shown in ‘blue’ and ‘green’ colours. (E) 2D visualization of the DCC matrix, colour-coded based on pairwise correlation values.

Figure 3.

(A) 3D network and structure view of M-box riboswitch (PDB: 2QBZ, chain X) shown. The nodes are coloured based on their connectivity (i.e. degree) with highly connected nodes depicted in ‘red’ colour. (B) 3D network and structure view of protein-DNA interface of human TATA box binding protein (PDB: 1CDW). The interface component with amino acids ‘KVFP’ (highlighted in red) is characteristic of β sheet–DNA interaction interface.