Comparison between slow anisotropic LE4PD fluctuations and the principal component analysis modes of ubiquitin

The biological function and folding mechanisms of proteins are often guided by large-scale slow motions, which involve crossing high energy barriers. In a simulation trajectory, these fluctuations commonly identified using principal component analysis (PCA). Despite the popularity this method, complete its predictions based on physics protein motion has been so far limited. This study formally connects PCA to Langevin model dynamics analyzes contributions barriers hydrodynamic interactions modes motion. To do so, we introduce an anisotropic extension equation for dynamics, called LE4PD-XYZ, “essential dynamics.” LE4PD-XYZ is accurate coarse-grained diffusive method motion, describes in alpha carbons protein. LE4PD accounts effects mode-dependent free-energy compares predictions, starting from microsecond-long carbon molecular atomistic trajectory ubiquitin. We observe that inclusion important identification timescales ubiquitin’s modes.