Biomolecular Dynamics @ Uni Freiburg

Vibrational Signatures of Biomolecular Dynamics

Modern techniques of infrared spectroscopy, in particular multidimensional and time-resolved version of it, have opened the way to monitor secondary structure and dynamics of polypeptides and proteins. In particular the amide I band, reflecting the backbone C=O stretching vibration, has been found to yield strucural information. To obtain a first principles description of the amide I vibrational spectrum of peptides in aqueous solution, we pursue a quantum-classical approach which consists of a classical molecular dynamics simulation of the conformational distribution of the system, density functional theory calculations of the conformation-dependent and solvent-induced frequency fluctuations, and a semiclassical description of the vibrational line shapes.

Real time observation of ultrafast peptide conformational dynamics: MD simulation vs. IR experiment

Employing nonequilibrium molecular dynamics (MD) simulations and transient infrared (IR) spectroscopy, a joint theoretical/experimental study on a water-soluble photoswitchable octapeptide designed by Renner et al. [Biopolymers 63, 382 (2002)] is presented. The simulations predict the cooling of the hot photoproducts on a time scale of 7 ps and complex conformational rearrangements ranging from a few picoseconds to several nanoseconds. The experiments yield a dominant fast relaxation time of 5 ps, which is identified as the cooling time of the peptide in water and also accounts for initial conformational changes of the system. Moreover, a weaker component of 300 ps is found, which reflects the overall conformational relaxation of the system. The virtues and the limitations of the joint MD/IR approach to describe biomolecular conformational rearrangements are discussed.
Real time observation of ultrafast peptide conformational dynamics: Molecular Dynamics simulation vs. Infrared experiment, P. H. Nguyen, H. Staudt, J. Wachtveitl, and G. Stock, J. Phys. Chem. B 115, 13084 (2011)

Simulation of transient infrared spectra of a photoswitchable peptide

In transient infrared (IR) experiments, a molecular system may be photoexcited in a nonstationary conformational state, whose time evolution is monitored via IR spectroscopy with high temporal and structural resolution. As a theoretical formulation of these experiments, this work derives explicit expressions for transient one- and two-dimensional IR spectra and discusses various levels of approximation and sampling strategies. Adopting a photoswitchable octapeptide in water as a representative example, nonequilibrium molecular dynamics simulations are performed and the photoinduced conformational dynamics and associated IR spectra are discussed in detail. Interestingly, it is found that the time scales of dynamics and spectra may differ from residue to residue by up to an order of magnitude. Considering merely the cumulative spectrum of all residues, the contributions of the individual residues largely compensate each other, which may explain the surprisingly small frequency shifts and short photoproduct rise times found in experiment. Even when a localized amide I mode is probed (e.g., via isotope labelling), the vibrational frequency shift is shown to depend in a complicated way on the conformation of the entire peptide as well as on the interaction with the solvent. In this context, various issues concerning the interpretation of transient IR spectra and conformational dynamics in terms of a few exponential time scales are discussed.
Simulation of transient infrared spectra of a photoswitchable peptide, M. Kobus, M. Lieder, P. H. Nguyen, and G. Stock, J. Chem. Phys. 135, 225102 (2011)

Infrared signatures of the peptide dynamical transition

Recent two-dimensional infrared (2D-IR) experiments on a short peptide 310-helix in chloroform solvent [Backus et al., J. Phys. Chem. B 113, 13405 (2009)] revealed an intriguing temperature dependence of the homogeneous line width, which was interpreted in terms of a dynamical transition of the peptide. To explain these findings, extensive molecular dynamics simulations at various temperatures were performed in order to construct the free energy landscape of the system. The study recovers the familiar picture of a glass-forming system, which below the glass transition temperature Tg is trapped in various energy basins, while it diffuses freely between these basins above Tg. In fact, one finds at Tg≈ 270 K a sharp rise of the fluctuations of the backbone dihedral angles, which reflects conformational transitions of the peptide. The corresponding C=O frequency fluctuations are found to be a sensitive probe of the peptide conformational dynamics from femtosecond to nanosecond time scales and lead to 2D-IR spectra that qualitatively match the experiment. The calculated homogeneous line width, however, does not show the biphasic temperature dependence observed in experiment. The discrepancy appears to be caused by the inappropriate modeling of the frequency shift of the chloroform solvent, which indicates the importance of solvent fluctuations for the peptide dynamical transition.
Free energy landscape ΔG (φ, ψ) (in kJ/mol) along the inner backbone dihedral angles φ and ψ of the Aib peptide, obtained for 220 and 300K.
(A) Short-time evolution of the total C=O frequency fluctuation  correlation function at 220 K (red) and 300 K (green). The curves are fitted by an exponential function, the weight (green) and decay  time τ (red) of which are shown in panel (B) as a function of temperature. The resulting total homogeneous dephasing rate (red) is shown in (C) together with the antidiagonal width of the 2D-IR spectra (green).
Infrared signatures of the peptide dynamical transition: A molecular dynamics simulation study, M. Kobus, P. H. Nguyen, and G. Stock, J. Chem. Phys. 133, 034512 (2010)