FAMUSAMM: An algorithm for rapid evaluation of electrostatic interactions in molecular dynamics simulations

A light-switchable peptide is transformed with ultrashort pulses from a ␤-hairpin to an unfolded hydrophobic cluster and vice versa. The structural changes are monitored by mid-IR probing. Instantaneous normal mode analysis with a Hamiltonian combining density functional theory with molecular mechanics is used to interpret the absorption transients. Illumination of the ␤-hairpin state triggers an unfolding reaction that visits several intermediates and reaches the unfolded state within a few nanoseconds. In this unfolding reaction to the equilibrium hydrophobic cluster conformation, the system does not meet significant barriers on the free-energy surface. The reverse folding process takes much longer because it occurs on the time scale of 30 s. The folded state has a defined structure, and its formation requires an extended search for the correct hydrogen-bond pattern of the ␤-strand.density functional theory calculation ͉ peptide folding ͉ TrpZip2 ͉ ultrafast infrared spectroscopy F olding is a key process during the formation of a functional protein after the synthesis of its amino acid chain (1). During folding, the amino acid chains are rearranged in highly complex processes, for which a detailed understanding is still missing. Straightforward solutions of the folding problem are prevented by the high dimensionality of the protein conformational spaces and by the wide range of relevant time scales. Thus, for complexity reduction, one has to focus on typical protein substructures, which are small enough to be analyzed by present-day technology. With corresponding peptide model systems there is a chance to monitor the formation of secondary structures, to identify characteristic intermediate states of these folding dynamics, and to carry out realistic simulations on a molecular level. An interesting class of model systems are light-triggered peptides, within which the incorporation of a photoresponsive element can initiate structural changes.Among corresponding photoresponsive chromophores, azobenzene derivatives have become a popular choice when it comes to selecting a fast conformational trigger for peptide refolding, because their structure significantly changes on time scales of a few hundred femtoseconds after photoexcitation. Indeed, an azobenzene chromophore, used as a backbone element within cyclic peptides, was shown to induce large-scale conformational changes, whose dynamics could be monitored by visible (2) and IR (3) spectroscopy. Moreover, the experimental results clearly showed that the initial, strongly driven conformational changes of the peptide proceeded within a few picoseconds after the trigger event. Externally linked to an ␣-helix, azobenzene also was used for unfolding (4) and refolding (5) of an ␣-helical model peptide in the nanosecond to microsecond time range.A prominent secondary structure motif is the ␤-sheet, for which a ␤-hairpin represents a minimal model (6, 7). We and others (8-10) have recently focused on the design of photocontrolled ␤-hairpin peptides. To enable an ultrafa...

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“…The covalent linkages between the peptide backbone and MM fragment (dye, side chains, and solvent) were treated as described in ref. 37.…”

Section: Methodsmentioning

confidence: 99%

Light-triggered β-hairpin folding and unfolding

Schrader

Schreier

Cordes

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…MSMD avoids the usual cutoff of the electrostatics. Instead, by using fast hierarchical multipole expansions (25,26), the electrostatic interactions are calculated explicitly up to a distance given by the minimum image convention relevant for periodic boundary systems and from a reaction field model at larger distances. Thus, MSMD substantially extends the approach suggested before (27).…”

Section: Methodsmentioning

confidence: 99%

Ultrafast spectroscopy reveals subnanosecond peptide conformational dynamics and validates molecular dynamics simulation

Spörlein

Carstens

Satzger

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

203

214

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Femtosecond time-resolved spectroscopy on model peptides with built-in light switches combined with computer simulation of light-triggered motions offers an attractive integrated approach toward the understanding of peptide conformational dynamics. It was applied to monitor the light-induced relaxation dynamics occurring on subnanosecond time scales in a peptide that was backbone-cyclized with an azobenzene derivative as optical switch and spectroscopic probe. The femtosecond spectra permit the clear distinguishing and characterization of the subpicosecond photoisomerization of the chromophore, the subsequent dissipation of vibrational energy, and the subnanosecond conformational relaxation of the peptide. The photochemical cis͞trans-isomerization of the chromophore and the resulting peptide relaxations have been simulated with molecular dynamics calculations. The calculated reaction kinetics, as monitored by the energy content of the peptide, were found to match the spectroscopic data. Thus we verify that all-atom molecular dynamics simulations can quantitatively describe the subnanosecond conformational dynamics of peptides, strengthening confidence in corresponding predictions for longer time scales.

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“…34) the distance class scheme of SAMM. 58,59,65 The extended scheme partitions the PMM environment of each DFT atom μ into disjoint distance classes C l μ , l = 0, . .…”

Section: B Dft/pmm With Samm Pmentioning

confidence: 99%

Coupling density functional theory to polarizable force fields for efficient and accurate Hamiltonian molecular dynamics simulations

Schwörer

Breitenfeld

Tröster

et al. 2013

The Journal of Chemical Physics

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Hybrid molecular dynamics (MD) simulations, in which the forces acting on the atoms are calculated by grid-based density functional theory (DFT) for a solute molecule and by a polarizable molecular mechanics (PMM) force field for a large solvent environment composed of several 10 3 -10 5 molecules, pose a challenge. A corresponding computational approach should guarantee energy conservation, exclude artificial distortions of the electron density at the interface between the DFT and PMM fragments, and should treat the long-range electrostatic interactions within the hybrid simulation system in a linearly scaling fashion. Here we describe a corresponding Hamiltonian DFT/(P)MM implementation, which accounts for inducible atomic dipoles of a PMM environment in a joint DFT/PMM self-consistency iteration. The long-range parts of the electrostatics are treated by hierarchically nested fast multipole expansions up to a maximum distance dictated by the minimum image convention of toroidal boundary conditions and, beyond that distance, by a reaction field approach such that the computation scales linearly with the number of PMM atoms. Short-range over-polarization artifacts are excluded by using Gaussian inducible dipoles throughout the system and Gaussian partial charges in the PMM region close to the DFT fragment. The Hamiltonian character, the stability, and efficiency of the implementation are investigated by hybrid DFT/PMM-MD simulations treating one molecule of the water dimer and of bulk water by DFT and the respective remainder by PMM. © 2013 AIP Publishing LLC. [http://dx

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FAMUSAMM: An algorithm for rapid evaluation of electrostatic interactions in molecular dynamics simulations

Cited by 67 publications

References 52 publications

Light-triggered β-hairpin folding and unfolding

Light-triggered β-hairpin folding and unfolding

Ultrafast spectroscopy reveals subnanosecond peptide conformational dynamics and validates molecular dynamics simulation

Coupling density functional theory to polarizable force fields for efficient and accurate Hamiltonian molecular dynamics simulations

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