High-Resolution Visualisation of the States and Pathways Sampled in Molecular Dynamics Simulations

Abstract

We have recently developed a scalable algorithm for ordering the instantaneous observations of a dynamical system evolving continuously in time. Here, we apply the method to long molecular dynamics trajectories. The procedure requires only a pairwise, geometrical distance as input. Suitable annotations of both structural and kinetic nature reveal the free energy basins visited by biomolecules. The profile is supplemented by a trace of the temporal evolution of the system highlighting the sequence of events. We demonstrate that the resultant SAPPHIRE (States And Pathways Projected with HIgh REsolution) plots provide a comprehensive picture of the thermodynamics and kinetics of complex, molecular systems exhibiting dynamics covering a range of time and length scales. Information on pathways connecting states and the level of recurrence are quickly inferred from the visualisation. The considerable advantages of our approach are speed and resolution: the SAPPHIRE plot is scalable to very large data sets and represents every single snapshot. This minimizes the risk of missing states because of overlap or prior coarse-graining of the data.

The ATAD2 bromodomain binds different acetylation marks on the histone H4 in similar fuzzy complexes

“…Different annotations of the trajectory can be plotted per snapshot as arranged by the progress index to obtain a SAP-PHIRE plot (48), which helps in the interpretation of the discovered basins. The cut function we show here for kinetic partitioning is the so-called local cut in the original publication (49).…”

“…To quantify the mutual similarity and level of overlap between the apo-and holo-runs, we turn to a powerful analysis and visualization strategy called a SAPPHIRE plot (48). Briefly, all snapshots are arranged by geometric criteria that use as the only input a definition of pairwise distance between conformations.…”

Peptide Binding to a PDZ Domain by Electrostatic Steering via Nonnative Salt Bridges

“…Recently, we have developed an algorithm for the analysis of long MD trajectories (46,47). The resulting SAPPHIRE (States And Pathways Projected with HIgh REsolution) plot is a comprehensive visualization of the thermodynamics and kinetics of the simulated system.…”

“…Table S1 in the Supporting Material contains the full list of atom pairs used. We briefly describe the method here and refer the reader to the original publications for more details (46,47). Starting from an arbitrary snapshot, all the snapshots are sequentially ordered in a stepwise fashion.…”

“…We have recently developed a method for the visualization of long MD trajectories (46,47). The main output of the method is the SAPPHIRE plot, which offers an intuitive illustration of the states and sequence of events encountered during the simulation (see Materials and Methods).…”