title: Contact- and distance-based principal component analysis of protein dynamics.
abstract: To interpret molecular dynamics simulations of complex systems, systematic dimensionality reduction methods such as principal component analysis (PCA) represent a well-established and popular approach. Apart from Cartesian coordinates, internal coordinates, e.g., backbone dihedral angles or various kinds of distances, may be used as input data in a PCA. Adopting two well-known model problems, folding of villin headpiece and the functional dynamics of BPTI, a systematic study of PCA using distance-based measures is presented which employs distances between Cα-atoms as well as distances between inter-residue contacts including side chains. While this approach seems prohibitive for larger systems due to the quadratic scaling of the number of distances with the size of the molecule, it is shown that it is sufficient (and sometimes even better) to include only relatively few selected distances in the analysis. The quality of the PCA is assessed by considering the resolution of the resulting free energy landscape (to identify metastable conformational states and barriers) and the decay behavior of the corresponding autocorrelation functions (to test the time scale separation of the PCA). By comparing results obtained with distance-based, dihedral angle, and Cartesian coordinates, the study shows that the choice of input variables may drastically influence the outcome of a PCA.
authors.affiliation: Biomolecular Dynamics, Institute of Physics, Albert Ludwigs University, 79104 Freiburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Ernst
authors.affiliation: Biomolecular Dynamics, Institute of Physics, Albert Ludwigs University, 79104 Freiburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Sittel
authors.affiliation: Biomolecular Dynamics, Institute of Physics, Albert Ludwigs University, 79104 Freiburg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Stock
mesh_terms: D007611:Aprotinin / Q000737:chemistry*; D008840:Microfilament Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D025341:Principal Component Analysis
chemical_list: D008840:Microfilament Proteins; C026615:villin; D007611:Aprotinin