Molecular Dynamics Force Field Parameters for the EGFP Chromophore and Some of Its Analogues
Year: 2023
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide Fluorescent proteins (FPs) have had an enormous impact on molecular and cellular biology and are employed in a wide range of studies of molecular structure and dynamics. Yet, only a modest number of papers have published molecular dynamics (MD) parameters describing FPs. And despite the development of a wide range of FPs, there has been no careful development of MD parameters across a series of FPs. In this work, we present MD parameters describing six fluorescent protein chromophores (EGFP, EBFP, EYFP, ECFP, mCherry, and DsRed) for use with the Cornell et al . ( J. Am. Chem. Soc. 1995, 117, 5179−5197) family of AMBER force fields, including ff14SB and ff19SB. We explore a wide range of solvent dielectric constants for determining the chromophore equilibrium geometry and evaluate the impact of the modeled solvent on the final atomic charges. We also present our methodological approach in which we considered all six chromophores together with a focus on modularity, transferability, and balance with existing force fields. The parameters given here make it easy to employ MD simulations to study any of the six systems, whereas the methodology makes it easy for anyone to extend this work to develop consistent parameters for additional fluorescent proteins. The results of our own MD simulations are presented, showing that the classical MD parameters yield chromophore structural distributions that compare well with QM/MM simulations.
Institution: Hope College
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Awards: G1104651672, G1438443317, RUI: Quantifying Fluorescent Probe Dynamics in FRET Experiments by Combining Single-Molecule and Bulk Spectroscopies with Molecular Dynamics and Quantum Mechanics Simulations, G4257795037, MRI: Acquisition of a High Performance Computing Cluster for Undergraduate Chemistry Research and Teaching by the Midwest Undergraduate Computational Chemistry Consortium (MU3C), MRI: Acquisition of a Computer Cluster for Undergraduate Chemistry Research and Teaching by the Midwest Undergraduate Computational Chemistry Consortium (MU3C), G6688081928, G812778616
OpenAlex ID: W4382010728