MOLE: A Voronoi Diagram-Based Explorer of Molecular Channels, Pores, and Tunnels

Abstract

We have developed an algorithm, "MOLE," for the rapid, fully automated location and characterization of molecular channels, tunnels, and pores. This algorithm has been made freely available on the Internet (http://mole.chemi.muni.cz/) and overcomes many of the shortcomings and limitations of the recently developed CAVER software. The core of our MOLE algorithm is a Dijkstra's path search algorithm, which is applied to a Voronoi mesh. Tests on a wide variety of biomolecular systems including gramicidine, acetylcholinesterase, cytochromes P450, potassium channels, DNA quadruplexes, ribozymes, and the large ribosomal subunit have demonstrated that the MOLE algorithm performs well. MOLE is thus a powerful tool for exploring large molecular channels, complex networks of channels, and molecular dynamics trajectories in which analysis of a large number of snapshots is required.

Structure of the monofunctional heme catalase DR1998 from Deinococcus radiodurans

“…Structure factors and associated structure coordinates were deposited in the Protein Data Bank in Europe [61]. The analysis of molecular channels was performed with CAVER [62,63] and MOLE [64].…”

The Role of Protein-Protein and Protein-Membrane Interactions on P450 Function

“…The active site, which is deeply buried in P450 structures Johnson and Stout, 2013), is above the membrane surface and is accessible through a network of access channels (Cojocaru et al, 2007). Analysis of access channels by software tools CAVER (Petrek et al, 2006) and MOLE (Petrek et al, 2007) showed that openings of activesite access channels are positioned inside the membrane and the solvent channel exit (passing between F and I helices) faces the water/ membrane interface (Fig. 9).…”

Implicit surfaces for interactive graph based cavity analysis of molecular simulations

“…Coleman and Sharp [2] improve the method in a way that the initialization step is automatized and the algorithm is able to find arbitrarily shaped tunnels. In CAVER [27] and MOLE [26], Petrek et al use Voronoi diagrams to discover molecular channels and pores. Recently Lindow et al [18] presented a technique that allows to extract significants paths from the molecules.…”

“…An important contribution is that we do not consider only position of atoms solely, like for instance in many Voronoi diagram approaches [19,26,35], but instead we put emphasis on the molecular surface itself. Additionally, thanks to implicit representation we are not bound to any fixed structure, as for instance in grid based discretization [14,27,34], but we are able to evaluate cavity distance parameters at any point in space with respect to the molecular isosurface.…”