Exploring High Dimensional Free Energy Landscapes: Temperature Accelerated Sliced Sampling

Biased sampling of collective variables is widely used to accelerate rare events in molecular simulations and to explore free energy surfaces. However, computational efficiency of these methods decreases with increasing number of collective variables, which severely limits the predictive power of the enhanced sampling approaches. Here we propose a method called Temperature Accelerated Sliced Sampling (TASS) that combines temperature accelerated molecular dynamics with umbrella sampling and metadynamics to sample the collective variable space in an efficient manner. The presented method can sample a large number of collective variables and is advantageous for controlled exploration of broad and unbound free energy basins. TASS is also shown to achieve quick free energy convergence and is practically usable with ab initio molecular dynamics techniques

Exploring the origins of the power-law properties of energy landscapes: An egg-box model

Multidimensional potential energy landscapes (PELs) have a Gaussian distribution for the energies of the minima, but at the same time the distribution of the hyperareas for the basins of attraction surrounding the minima follows a power-law. To explore how both these features can simultaneously be true, we introduce an ``egg-box'' model. In these model landscapes, the Gaussian energy distribution is used as a starting point and we examine whether a power-law basin area distribution can arise as a natural consequence through the swallowing up of higher-energy minima by larger low-energy basins when the variance of this Gaussian is increased sufficiently. Although the basin area distribution is substantially broadened by this process,it is insufficient to generate power-laws, highlighting the role played by the inhomogeneous distribution of basins in configuration space for actual PELs.Comment: 7 pages, 8 figure

Exploring the Free Energy Landscape: From Dynamics to Networks and Back

The knowledge of the Free Energy Landscape topology is the essential key to understand many biochemical processes. The determination of the conformers of a protein and their basins of attraction takes a central role for studying molecular isomerization reactions. In this work, we present a novel framework to unveil the features of a Free Energy Landscape answering questions such as how many meta-stable conformers are, how the hierarchical relationship among them is, or what the structure and kinetics of the transition paths are. Exploring the landscape by molecular dynamics simulations, the microscopic data of the trajectory are encoded into a Conformational Markov Network. The structure of this graph reveals the regions of the conformational space corresponding to the basins of attraction. In addition, handling the Conformational Markov Network, relevant kinetic magnitudes as dwell times or rate constants, and the hierarchical relationship among basins, complete the global picture of the landscape. We show the power of the analysis studying a toy model of a funnel-like potential and computing efficiently the conformers of a short peptide, the dialanine, paving the way to a systematic study of the Free Energy Landscape in large peptides.Comment: PLoS Computational Biology (in press

Landscape and flux for quantifying global stability and dynamics of game theory

Game theory has been widely applied to many areas including economics, biology and social sciences. However, it is still challenging to quantify the global stability and global dynamics of the game theory. We developed a landscape and flux framework to quantify the global stability and global dynamics of the game theory. As an example, we investigated the models of three-strategy games: a special replicator-mutator game, the repeated prison dilemma model. In this model, one stable state, two stable states and limit cycle can emerge under different parameters. The repeated Prisoner's Dilemma system has Hopf bifurcation transitions from one stable state to limit cycle state, and then to another one stable state or two stable states, or vice versa. We explored the global stability of the repeated Prisoner's Dilemma system and the kinetic paths between the basins of attractor. The paths are irreversible due to the non-zero flux. One can explain the game for $Peace$ and $War$.Comment: 25 pages, 15 figure

Exploring constrained quantum control landscapes

The broad success of optimally controlling quantum systems with external fields has been attributed to the favorable topology of the underlying control landscape, where the landscape is the physical observable as a function of the controls. The control landscape can be shown to contain no suboptimal trapping extrema upon satisfaction of reasonable physical assumptions, but this topological analysis does not hold when significant constraints are placed on the control resources. This work employs simulations to explore the topology and features of the control landscape for pure-state population transfer with a constrained class of control fields. The fields are parameterized in terms of a set of uniformly spaced spectral frequencies, with the associated phases acting as the controls. Optimization results reveal that the minimum number of phase controls necessary to assure a high yield in the target state has a special dependence on the number of accessible energy levels in the quantum system, revealed from an analysis of the first- and second-order variation of the yield with respect to the controls. When an insufficient number of controls and/or a weak control fluence are employed, trapping extrema and saddle points are observed on the landscape. When the control resources are sufficiently flexible, solutions producing the globally maximal yield are found to form connected `level sets' of continuously variable control fields that preserve the yield. These optimal yield level sets are found to shrink to isolated points on the top of the landscape as the control field fluence is decreased, and further reduction of the fluence turns these points into suboptimal trapping extrema on the landscape. Although constrained control fields can come in many forms beyond the cases explored here, the behavior found in this paper is illustrative of the impacts that constraints can introduce.Comment: 10 figure

Experimental exploration over a quantum control landscape through nuclear magnetic resonance

The growing successes in performing quantum control experiments motivated the development of control landscape analysis as a basis to explain these findings.When a quantum system is controlled by an electromagnetic field, the observable as a functional of the control field forms a landscape. Theoretical analyses have revealed many properties of control landscapes, especially regarding their slopes, curvatures, and topologies. A full experimental assessment of the landscape predictions is important for future consideration of controlling quantum phenomena. Nuclear magnetic resonance (NMR) is exploited here as an ideal laboratory setting for quantitative testing of the landscape principles. The experiments are performed on a simple two-level proton system in a H$_2$O-D$_2$O sample. We report a variety of NMR experiments roving over the control landscape based on estimation of the gradient and Hessian, including ascent or descent of the landscape, level set exploration, and an assessment of the theoretical predictions on the structure of the Hessian. The experimental results are fully consistent with the theoretical predictions. The procedures employed in this study provide the basis for future multispin control landscape exploration where additional features are predicted to exist