Coherent multidimensional vibrational spectroscopy of biomolecules: concepts, simulations, and challenges

The response of complex molecules to sequences of femtosecond infrared pulses provides a unique window into their structure, dynamics, and fluctuating environments. Herein we survey the basic principles of modern two-dimensional infrared (2DIR) spectroscopy, which analogous to those of multidimensional NMR spectroscopy. The perturbative approach for computing the nonlinear optical response of coupled localized chromophores is introduced and applied to the amide backbone transitions of proteins, liquid water, membrane lipids, and amyloid fibrils. The signals are analyzed using classical molecular dynamics simulations combined with an effective fluctuating Hamiltonian for coupled localized anharmonic vibrations whose dependence on the local electrostatic environment is parameterized by an ab initio map. Several simulation methods, (cumulant expansion of Gaussian fluctuation, quasiparticle scattering, the stochastic Liouville equations, direct numerical propagation) are surveyed. Chirality-induced techniques which dramatically enhance the resolution are demonstrated. Signatures of conformational and hydrogen-bonding fluctuations, protein folding, and chemical-exchange processes are discussed.