Analyzing protein topology based on Laguerre tessellation of a pore-traversing water network

Abstract

Given the tight relation between protein structure and function, we present a set of methods to analyze protein topology, implemented in the VLDP program, relying on Laguerre space partitions built from series of molecular dynamics snapshots. The Laguerre partition specifies inter-atomic contacts, formalized in graphs. The deduced properties are the existence and count of water aggregates, possible passage ways and constrictions, the structure, connectivity, stability and depth of the water network. As a test-case, the membrane protein FepA is investigated in its full environment, yielding a more precise description of the protein surface. Inside FepA, the solvent splits into isolated clusters and an intricate network connecting both sides of the lipid bilayer. The network is dynamic, connections set on and off, occasionally substantially relocating traversing paths. Subtle differences are detected between two forms of FepA, ligand-free and complexed with its natural iron carrier, the enterobactin. The complexed form has more constricted and more centered openings in the upper part whereas, in the lower part, constriction is released: two main channels between the plug and barrel lead directly to the periplasm. Reliability, precision and the variety of topological features are the main interest of the method.

Using Computer Simulations and Virtual Reality to Understand, Design and Optimize Artificial Water Channels

“…One-dimensional water wires in particular have attracted broad interest with selective proton gating being the key function of the Influenza A M2 proton channel [12,13]. Entrapped water clusters within complex structures are a key element intervening in a variety of fundamental processes such as water structuration related to water-water or water-host-matrix interactions under confined conditions [47], selective transport of small metabolites [52], and in context of dynamic diffusion phenomena [14][15][16][17] of water molecules across the channels [17,48]. So far, only a few artificial hydrophobic [29], hydrophilic [7][8][9] or amphiphilic pores [30,31] have been designed to selectively and efficiently transport water through bilayer membranes.…”

Visualizing Biological Membrane Organization and Dynamics

“…Image-processing techniques (Figure 15D) are another source of specific membrane analysis tools, as applied to detection of lipid phases during phase separation [269]. Concerning membrane proteins, the analysis of helix geometry and its visual abstraction (Figure 15E) were proposed [270] as well as the characterization of their particular topologies (Figure 15F), notably in relation to water networks prefiguring solute transport, based on Laguerre tesselation [271].…”

“…E: Bendix membrane protein helix representations colored by an angle-indicative heatmap [270]. F: Laguerre tesselation analysis of the water network through the FepA membrane protein showing a water path through the protein bridging the media on both sides of the membrane (left) and isolated water inclusions (centre) with an inset zooming in on a selected inclusion [271].…”

Visualizing Biological Membrane Organization and Dynamics

“…E: Bendix membrane protein helix representations colored by an angle-indicative heatmap [270]. F: Laguerre tesselation analysis of the water network through the FepA membrane protein showing a water path through the protein bridging the media on both sides of the membrane (left) and isolated water inclusions (centre) with an inset zooming in on a selected inclusion [271]. Figure 16: Selected historic illustrations from the literature.…”