Solvent induced conformational fluctuation of alanine dipeptide studied by using vibrational probes

•Implicit solvent induced potential energy fluctuation and the stability of ALAD is revealed.•Conformational dependence of the amide I frequencies of ALAD in different implicit solvents is investigated.•The solvated structure of ALAD is revealed in explicit solvents using MD simulations.•The combination of explicit solvent in the first hydration shell and implicit solvent in the bulk is applied for ALAD.

The solvation effect on the three dimensional structure and the vibrational feature of alanine dipeptide (ALAD) was evaluated by applying the implicit solvents from polarizable continuum solvent model (PCM) through ab initio calculations, by using molecular dynamic (MD) simulations with explicit solvents, and by combining these two approaches. The implicit solvent induced potential energy fluctuations of ALAD in CHCl3, DMSO and H2O are revealed by means of ab initio calculations, and a global view of conformational and solvation environmental dependence of amide I frequencies is achieved. The results from MD simulations with explicit solvents show that ALAD trends to form PPII, αL, αR, and C5 in water, PPII and C5 in DMSO, and C5 in CHCl3, ordered by population, and the demonstration of the solvated structure, the solute–solvent interaction and hydrogen bonding is therefore enhanced. Representative ALAD–solvent clusters were sampled from MD trajectories and undergone ab initio calculations. The explicit solvents reveal the hydrogen bonding between ALAD and solvents, and the correlation between amide I frequencies and the CO bond length is built. The implicit solvents applied to the ALAD–solvent clusters further compensate the solvation effect from the bulk, and thus enlarge the degree of structural distortion and the amide I frequency red shift. The combination of explicit solvent in the first hydration shell and implicit solvent in the bulk is helpful for our understanding about the conformational fluctuation of solvated polypeptides through vibrational probes.

Graphical abstractThe solvent induced conformational fluctuation and frequency shift of amide I modes were examined by the combination of explicit and implicit solvent models.Figure optionsDownload full-size imageDownload as PowerPoint slide