Explicit proton transfer in classical molecular dynamics simulations

Wolf, Maarten G.; Groenhof, Gerrit

doi:10.1002/jcc.23536

Cited by 39 publications

(42 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although de-activation of fluorescence also requires protonation, it was shown by Van Thor and co-workers 5b that this occurs after the isomerization and at timescales beyond reach of our QM/MM simulations. We therefore will address the protonation process in the future, using either a classical approach for proton transfer, 14 a combination of empirical valence bond theory 15 and the QCFF/PI model, 16,17 or by means of QM/MM pKa calculations. 18 Inspection of the starting geometries revealed that rapid photoisomerization occurs only if the phenolate oxygen of the chromophore accepts at most one hydrogen bond from the environment, whereas no deactivation was observed if there are two or more hydrogen bonds.…”

Section: Hydrogen Bond Fluctuations Control Photochromism In a Reversmentioning

confidence: 99%

Hydrogen Bond Fluctuations Control Photochromism in a Reversibly Photo‐Switchable Fluorescent Protein

Morozov

Groenhof

2015

Angewandte Chemie

Self Cite

View full text Add to dashboard Cite

Reversibly switchable fluorescent proteins (RSFPs) are essential for high‐resolution microscopy of biological samples, but the reason why these proteins are photochromic is still poorly understood. To address this problem, we performed molecular dynamics simulations of the fast switching Met159Thr mutant of the RSFP Dronpa. Our simulations revealed a ground state structural heterogeneity in the chromophore pocket that consists of three populations with one, two, or three hydrogen bonds to the phenolate moiety of the chromophore. By means of non‐adiabatic quantum mechanics/molecular dynamics simulations, we demonstrated that the subpopulation with a single hydrogen bond is responsible for off‐switching through photo‐isomerization of the chromophore, whereas two or more hydrogen bonds inhibit the isomerization and promote fluorescence instead. While rational design of new RSFPs has so far focused on structure alone, our results suggest that structural heterogeneity must be considered as well.

show abstract

Section: Hydrogen Bond Fluctuations Control Photochromism In a Reversmentioning

confidence: 99%

Hydrogen Bond Fluctuations Control Photochromism in a Reversibly Photo‐Switchable Fluorescent Protein

Morozov

Groenhof

2015

Angewandte Chemie

Self Cite

View full text Add to dashboard Cite

show abstract

“…A number of classical nonpolarizable models for hydronium have been proposed 39,45,77–79 . We tentatively chose the model proposed by Sagnella & Voth 77 with partial charges of −0.755 e on the O and +0.585 e on the H. The Lennard-Jones parameters were set equal to those of TIP3P water.…”

Section: Resultsmentioning

confidence: 99%

“…Applications have included GFP 40 , aquaporin 41 , acetic acid titration in water 42 , Fo-ATPase 43 and Nafion membranes 44 . Issues noted include the violation of detailed balance 45 , and an inability to study multiple protons due to integration instabilities 44 . A similar algorithm that also violates detailed balance uses a set of six geometric and energetic criteria to accept a hop and performs a local structure adjustment after each hop 46 .…”

Section: Introductionmentioning

confidence: 99%

Classical Molecular Dynamics with Mobile Protons

Lazaridis

Hummer

2017

J. Chem. Inf. Model.

View full text Add to dashboard Cite

An important limitation of standard classical molecular dynamics simulations is the inability to make or break chemical bonds. This restricts severely our ability to study processes that involve even the simplest of chemical reactions, the transfer of a proton. Existing approaches for allowing proton transfer in the context of classical mechanics are rather cumbersome and have not achieved widespread use and routine status. Here we reconsider the combination of molecular dynamics with periodic stochastic proton hops. To ensure computational efficiency, we propose a non-Boltzmann acceptance criterion that is heuristically adjusted to maintain the correct or desirable thermodynamic equilibria between different protonation states and proton transfer rates. Parameters are proposed for hydronium, Asp, Glu, and His. The algorithm is implemented in the program CHARMM and tested on proton diffusion in bulk water and carbon nanotubes, and on proton conductance in the gramicidin A channel. Using hopping parameters determined from proton diffusion in bulk water, the model reproduces the enhanced proton diffusivity in carbon nanotubes and gives a reasonable estimate of the proton conductance in gramicidin A.

show abstract

“…246 A field by itself is the investigation of proton transfer in bulk water for which a myriad of FF-based techniques have been developed. [247][248][249][250][251][252][253] Finally, modern electronic structure methods may pave the way for ab initio MD simulations of large systems on extended time scales. They include hypertensor contractions 254 or density renormalization group techniques.…”

Section: Discussionmentioning

confidence: 99%

Reactive molecular dynamics: From small molecules to proteins

Meuwly

2018

WIREs Comput Mol Sci

View full text Add to dashboard Cite

The current status of reactive molecular dynamics (MD) simulations is summarized. Both, methodological aspects and applications to problems ranging from gas phase reaction dynamics to ligand‐binding in solvated proteins are discussed, focusing on extracting information from simulations that cannot easily be obtained from experiments alone. One specific example is the structural interpretation of the ligand rebinding time scales extracted from state‐of‐the art time‐resolved experiments. Atomistic simulations employing validated reactive interaction potentials are capable of providing structural information about the time scales involved. Both, merits and shortcomings of the various methods are discussed and the outlook summarizes possible future avenues such as reactive potentials based on machine learning techniques. This article is categorized under: Molecular and Statistical Mechanics > Molecular Dynamics and Monte‐Carlo Methods Theoretical and Physical Chemistry > Reaction Dynamics and Kinetics Molecular and Statistical Mechanics > Molecular Interactions

show abstract

Explicit proton transfer in classical molecular dynamics simulations

Cited by 39 publications

References 89 publications

Hydrogen Bond Fluctuations Control Photochromism in a Reversibly Photo‐Switchable Fluorescent Protein

Hydrogen Bond Fluctuations Control Photochromism in a Reversibly Photo‐Switchable Fluorescent Protein

Classical Molecular Dynamics with Mobile Protons

Reactive molecular dynamics: From small molecules to proteins

Contact Info

Product

Resources

About