Deciphering environment effects in peptide bond solvation dynamics by experiment and theory

Abstract

Most proteins work in aqueous solution and the interaction with water strongly affects their structure and function. However, experimentally the motion of a specific single water molecule is difficult to trace by conventional methods, because they average over the heterogeneous solvation structure of bulk water surrounding the protein. Here, we provide a detailed atomistic picture of the water rearrangement dynamics around the -CONH- peptide linkage in the two model systems formanilide and acetanilide, which simply differ by the presence of a methyl group at the peptide linkage. The combination of picosecond pump-probe time-resolved infrared spectroscopy and molecular dynamics simulations demonstrates that the solvation dynamics at the molecular level is strongly influenced by this small structural difference. The effective timescales for solvent migration triggered by ionization are mainly controlled by the efficiency of the kinetic energy redistribution rather than the shape of the potential energy surface. This approach provides a fundamental understanding of protein hydration and may help to design functional molecules in solution with tailored properties.

Real-time observation of photoionization-induced water migration dynamics in 4-methylformanilide–water by picosecond time-resolved infrared spectroscopy and ab initio molecular dynamics simulations

“…This overshooting motion is settled down within around 10 ps by vibrational energy transfer to low-frequency intramolecular vibrations of tFA + . 24 The migration dynamics in the related tAA + -W(CO) cluster has been also simulated, and the twice faster migration than in tFA + -W is well reproduced (Figure 1). 21 tAA is a methyl-substituted derivative of tFA and thus the faster migration can be rationalized by the effect of the CH 3 group.…”

“…The latter are simulated according to the procedure that has been presented previously (for details see Ref. 21,24,36,37 ). Briefly, the ps-TRIR spectrum is expressed as a trajectory average with the envelope of a FWHM of 3 ps were employed.…”

“…19 To circumvent the problem of inhomogeneous water molecules, we have been working on hydration dynamics at a single solvent molecular level by probing solvated clusters in the gas phase using time-resolved infrared (TRIR) spectroscopy and advanced ab initio molecular dynamics (MD) simulations. [20][21][22][23][24][25] This approach offers size-and isomer-selectivity as well as full control over solvation structure and energy in the cluster.…”

“…The dynamics is typically initiated by UV laser excitation / photoionization of the clusters, and migration of the water molecule is monitored by changes in the TRIR spectra at the picosecond (ps) time scale. This technique of UV-UV ( ′ ) -IR ps time-resolved IR (ps-TRIR) spectroscopy combined with mass spectrometry has been successfully applied to a variety of monohydrated clusters, including the single water CO → NH migration around the peptide linkage in trans-acetanilide (tAA) 20,21 and trans-formanilide (tFA), 24 the CN → NH migration around 4-aminobenzonitrile, 22 and the NH → OH migration in 5-hydroxyindole. 25 Surprisingly, the lifetimes of these single water migrations vary over four orders of magnitude, ranging from 4 ps to 53 ns.…”

“…For example, the ab initio "on-the-fly" MD simulations reproduce the time-evolutions (TEs) obtained by the ps-TRIR spectra on monohydrated clusters of tAA and tFA (tAA-W and tFA-W), and visualize the migration trajectories of water as shown in Figure 1. 21,24 The water migration in tFA + -W(CO) (hereafter, W(CO) and W(NH) mean the water molecule bound to the CO and NH sites, respectively) triggered by photoionization of the aromatic chromophore proceeds in the molecular plane. The water molecule released from the initial CO binding site migrates toward the final NH site, but overshoots and moves like a largeamplitude damped pendulum around the NH destination site.…”