Value of Temporal Information When Analyzing Reaction Coordinates.

Reaction coordinates chart pathways from reactants to products of chemical reactions. Determination of reaction coordinates from ensembles of molecular trajectories has thus been the focus of many studies. A widely used and insightful choice of a reaction coordinate is the committor function, defined as the probability that a trajectory will reach the product before the reactant. Here, we consider alternatives to the committor function that add useful mechanistic information, the mean first passage time, and the exit time to the product. We further derive a simple relationship between the functions of the committor, the mean first passage time, and the exit time. We illustrate the diversity of mechanisms predicted by alternative reaction coordinates with several toy problems and with a simple model of protein searching for a specific DNA motif.

Probing Translocation in Mutants of the Anthrax Channel: Atomically Detailed Simulations with Milestoning.

Anthrax toxin consists of a cation channel and two protein factors. Translocation of the anthrax protein factors from endosomal to the cytosolic compartment is a complex process which utilizes the cation channel. An atomically detailed understanding of the function of the anthrax translocation machinery is incomplete. We report atomically detailed simulations of the lethal factor and channel mutants. Kinetic and thermodynamic properties of early events in the translocation process are computed within the Milestoning theory and algorithm. Several mutants of the channel illustrate that long-range electrostatic interactions provide the dominant driving force for translocation. No external energy input is required because the lower pH in the endosome relative to the cytosol drives the initial translocation process forward. Channel mutants with variable sizes cause smaller effects on translocation events relative to charge manipulations. Comparison with available experimental data is provided.

The Impact of Protonation on Early Translocation of Anthrax Lethal Factor: Kinetics from Molecular Dynamics Simulations and Milestoning Theory.

We report atomically detailed molecular dynamics simulations of the permeation of the lethal factor (LF) N-terminal segment through the anthrax channel. The N-terminal chain is unstructured and leads the permeation process for the LF protein. The simulations were conducted in explicit solvent with milestoning theory, making it possible to extract kinetic information from nanosecond to millisecond time scales. We illustrate that the initial event is strongly influenced by the protonation states of the permeating amino acids. While the N-terminal segment passes easily at high protonation state through the anthrax channel (and the ϕ clamp), the initial permeation represents a critical step, which can be irreversible and establishes a hook in the channel mouth.

Calculating Iso-Committor Surfaces as Optimal Reaction Coordinates with Milestoning.

Reaction coordinates are vital tools for qualitative and quantitative analysis of molecular processes. They provide a simple picture of reaction progress and essential input for calculations of free energies and rates. Iso-committor surfaces are considered the optimal reaction coordinate. We present an algorithm to compute efficiently a sequence of isocommittor surfaces. These surfaces are considered an optimal reaction coordinate. The algorithm analyzes Milestoning results to determine the committor function. It requires only the transition probabilities between the milestones, and not transition times. We discuss the following numerical examples: (i) a transition in the Mueller potential; (ii) a conformational change of a solvated peptide; and (iii) cholesterol aggregation in membranes.

Structural distortion in graphitic-C3N4 realizing an efficient photoreactivity.

Introducing structural distortion to semiconductors can dramatically modify their electronic structures, resulting in efficient separation of electron-hole pairs and achieving high photocatalytic activity of catalysts. Herein, we systematically studied the role that structural distortion played in the photocatalytic process by taking graphitic-C3N4 (g-C3N4) as an example, where the structural distortion can be introduced by elemental doping and heat treatment. Through the controllable structural distortion engineering, the photocatalytic activity of g-C3N4 can be significantly improved, which benefits from the effective separation of photogenerated electron-hole pairs, showing intriguing structural distortion-dependent photocatalytic activity. This study not only offers a new insight into the in-depth understanding of the effect of structural distortion on the photoreactivity of catalysts, but also provides a new pathway for designing advanced photocatalysts.