Comparing the Ability of Enhanced Sampling Molecular Dynamics Methods to Reproduce the Behavior of Fluorescent Labels on Proteins
MetadataShow full item record
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.
Showing items related by title, author, creator and subject.
Deplazes, Evelyne; Jayatilaka, D.; Corry, B. (2011)Fluorescence resonance energy transfer (FRET) is commonly used to determine the proximity of fluorophores, but usually many assumptions are required to gain a quantitative relationship between the likelihood of energy ...
Gandhi, Neha Sureshchandra (2011)Glycosaminoglycans (GAGs) are ubiquitous complex carbohydrate molecules present on the cell surfaces and in extracellular matrices (ECM) of vertebrate and invertebrate tissues. The interactions of sulphated GAGs such as ...
Molecular dynamics simulation of tau peptides for the investigation of conformational changes induced by specific phosphorylation patternsGandhi, N.; Kukic, P.; Lippens, G.; Mancera, Ricardo (2017)The Tau protein plays an important role due to its biomolecular interactions in neurodegenerative diseases. The lack of stable structure and various posttranslational modifications such as phosphorylation at various sites ...