Integrating Molecular Dynamics Simulations and Single-molecule FRET Spectroscopy: From Computational FRET Estimation to Experimental Data Interpretation

整合分子动力学模拟和单分子FRET光谱:从计算FRET估计到实验数据解释

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Abstract

Molecular dynamics (MD) simulations can characterize biomolecular processes at an exceptional spatiotemporal resolution not able to be accessed experimentally. As the limitations associated with MD simulations lessen and the method advances toward greater capabilities, the simulations are being applied to a wide array of new applications. For example, the integration of MD simulations and single-molecule Förster resonance energy transfer (smFRET) spectroscopy is a newly developing and growing application combining experimental and computational approaches. The integration of these techniques provides valuable insight into the conformational dynamics of biomolecules on an atomic-level, thereby enhancing the understanding of complex biological processes. This review compiles information on simulating FRET dyes and estimating FRET efficiencies from MD simulations and using MD simulations to gain insight into experimental data to shine light on the recent advancements in joining computational and experimental techniques. We discuss notable studies that incorporate the use of both MD simulations and smFRET as well as discuss the challenges that have been faced regarding their integration. The joining of these approaches have provided valuable insights into conformational sampling, binding mechanisms, structural dynamics, and allosteric effects thus far and will continue to advance the understanding of biomolecular dynamics in the future.

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