title: Construction of the free energy landscape of biomolecules via dihedral angle principal component analysis.
abstract: A systematic approach to construct a low-dimensional free energy landscape from a classical molecular dynamics (MD) simulation is presented. The approach is based on the recently proposed dihedral angle principal component analysis (dPCA), which avoids artifacts due to the mixing of internal and overall motions in Cartesian coordinates and circumvents problems associated with the circularity of angular variables. Requiring that the energy landscape reproduces the correct number, energy, and location of the system's metastable states and barriers, the dimensionality of the free energy landscape (i.e., the number of essential components) is obtained. This dimensionality can be determined from the distribution and autocorrelation of the principal components. By performing an 800 ns MD simulation of the folding of hepta-alanine in explicit water and using geometric and kinetic clustering techniques, it is shown that a five-dimensional dPCA energy landscape is a suitable and accurate representation of the full-dimensional landscape. In the second step, the dPCA energy landscape can be employed (e.g., in a Langevin simulation) to facilitate a detailed investigation of biomolecular dynamics in low dimensions. Finally, several ways to visualize the multidimensional energy landscape are discussed.
authors.affiliation: Institute of Physical and Theoretical Chemistry, J. W. Goethe University, Max-von-Laue-Strasse 7, D-60438 Frankfurt, Germany.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Altis
authors.forename: Moritz
authors.initials: M
authors.lastname: Otten
authors.forename: Phuong H
authors.initials: PH
authors.lastname: Nguyen
authors.forename: Rainer
authors.initials: R
authors.lastname: Hegger
authors.forename: Gerhard
authors.initials: G
authors.lastname: Stock
mesh_terms: D000409:Alanine; D003198:Computer Simulation; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D009842:Oligopeptides / Q000737:chemistry*; D025341:Principal Component Analysis; D013816:Thermodynamics
chemical_list: D009842:Oligopeptides; D000409:Alanine