title: Comparing the Ability of Enhanced Sampling Molecular Dynamics Methods To Reproduce the Behavior of Fluorescent Labels on Proteins.
abstract: Adequately sampling the large number of conformations accessible to proteins and other macromolecules is one of the central challenges in molecular dynamics (MD) simulations; this activity can be difficult, even for relatively simple systems. An example where this problem arises is in the simulation of dye-labeled proteins, which are now being widely used in the design and interpretation of Förster resonance energy transfer (FRET) experiments. In this study, MD simulations are used to characterize the motion of two commonly used FRET dyes attached to an immobilized chain of polyproline. Even in this simple system, the dyes exhibit complex behavior that is a mixture of fast and slow motions. Consequently, very long MD simulations are required to sufficiently sample the entire range of dye motion. Here, we compare the ability of enhanced sampling methods to reproduce the behavior of fluorescent labels on proteins. In particular, we compared Accelerated Molecular Dynamics (AMD), metadynamics, Replica Exchange Molecular Dynamics (REMD), and High Temperature Molecular Dynamics (HTMD) to equilibrium MD simulations. We find that, in our system, all of these methods improve the sampling of the dye motion, but the most significant improvement is achieved using REMD.
authors.affiliation: In Silico Numerical Laboratory and Institute of Experimental Physics, University of Gdansk , 80-952 Gdańsk, Poland.|Research School of Biology, Australian National University , Acton ACT 2601, Australia.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Walczewska-Szewc
authors.affiliation: Institute for Molecular Bioscience and School of Chemistry & Molecular Biosciences, The University of Queensland , Brisbane QLD 4072, Australia.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Deplazes
authors.affiliation: Research School of Biology, Australian National University , Acton ACT 2601, Australia.
authors.forename: Ben
authors.initials: B
authors.lastname: Corry
mesh_terms: D005453:Fluorescence; D031541:Fluorescence Resonance Energy Transfer; D005456:Fluorescent Dyes / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry*
chemical_list: D005456:Fluorescent Dyes; D010455:Peptides; C011083:polyproline