t-Distributed Stochastic Neighbor Embedding Method with the Least Information Loss for Macromolecular Simulations.

Dimensionality reduction methods are usually applied on molecular dynamics simulations of macromolecules for analysis and visualization purposes. It is normally desired that suitable dimensionality reduction methods could clearly distinguish functionally important states with different conformations for the systems of interest. However, common dimensionality reduction methods for macromolecules simulations, including predefined order parameters and collective variables (CVs), principal component analysis (PCA), and time-structure based independent component analysis (t-ICA), only have limited success due to significant key structural information loss. Here, we introduced the t-distributed stochastic neighbor embedding (t-SNE) method as a dimensionality reduction method with minimum structural information loss widely used in bioinformatics for analyses of macromolecules, especially biomacromolecules simulations. It is demonstrated that both one-dimensional (1D) and two-dimensional (2D) models of the t-SNE method are superior to distinguish important functional states of a model allosteric protein system for free energy and mechanistic analysis. Projections of the model protein simulations onto 1D and 2D t-SNE surfaces provide both clear visual cues and quantitative information, which is not readily available using other methods, regarding the transition mechanism between two important functional states of this protein.