Comparing the Ability of Enhanced Sampling Molecular Dynamics Methods to Reproduce the Behavior of Fluorescent Labels on Proteins
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...
| Main Authors: | , , |
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| Format: | Journal Article |
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American Chemical Society
2015
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| Online Access: | http://hdl.handle.net/20.500.11937/17950 |
| _version_ | 1848749606109708288 |
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| author | Walczewska-Szewc, K. Deplazes, Evelyne Corry, B. |
| author_facet | Walczewska-Szewc, K. Deplazes, Evelyne Corry, B. |
| author_sort | Walczewska-Szewc, K. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T07:23:36Z |
| format | Journal Article |
| id | curtin-20.500.11937-17950 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:23:36Z |
| publishDate | 2015 |
| publisher | American Chemical Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-179502017-09-13T15:42:22Z Comparing the Ability of Enhanced Sampling Molecular Dynamics Methods to Reproduce the Behavior of Fluorescent Labels on Proteins Walczewska-Szewc, K. Deplazes, Evelyne Corry, B. 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. 2015 Journal Article http://hdl.handle.net/20.500.11937/17950 10.1021/acs.jctc.5b00205 American Chemical Society restricted |
| spellingShingle | Walczewska-Szewc, K. Deplazes, Evelyne Corry, B. Comparing the Ability of Enhanced Sampling Molecular Dynamics Methods to Reproduce the Behavior of Fluorescent Labels on Proteins |
| title | Comparing the Ability of Enhanced Sampling Molecular Dynamics Methods to Reproduce the Behavior of Fluorescent Labels on Proteins |
| title_full | Comparing the Ability of Enhanced Sampling Molecular Dynamics Methods to Reproduce the Behavior of Fluorescent Labels on Proteins |
| title_fullStr | Comparing the Ability of Enhanced Sampling Molecular Dynamics Methods to Reproduce the Behavior of Fluorescent Labels on Proteins |
| title_full_unstemmed | Comparing the Ability of Enhanced Sampling Molecular Dynamics Methods to Reproduce the Behavior of Fluorescent Labels on Proteins |
| title_short | Comparing the Ability of Enhanced Sampling Molecular Dynamics Methods to Reproduce the Behavior of Fluorescent Labels on Proteins |
| title_sort | comparing the ability of enhanced sampling molecular dynamics methods to reproduce the behavior of fluorescent labels on proteins |
| url | http://hdl.handle.net/20.500.11937/17950 |