Dynamical Structures And Vibrational Spectrums Of Polypeptides In Solution Phase

The amide-I mode of polypeptide usually presents a strong broad band in mid-IR region which has been proven to be a useful structural probe for protein,since it is secondary structural sensitive.The understanding of dynamic structure of polypeptides is important for revealing their conformational dynamic and would be helpful for the understanding of the pathogenic mechanism of conformational disease caused by misfolding of polypeptide.In this paper,we aimed to reveal instantaneous secondary structure and conformational changes of polypeptides in solution.The enhanced sampling molecular dynamic simulations were also performed for the investigation of the dynamical structures of polypeptide and its azido-modification derivatives in solution for the comprehension of structural distribution of polypeptide.The research contents are as follows:1.The electrostatic effect from peptide backbone and chemical environment were investigated and correlated to the amide-I frequency difference of N-ethylpropionamide(NEPA)from gas phase to solution phase,two frequency maps were respectively built for this ?-peptide analogue in three kinds of solvents under different theoretical scheme(molecular mechanics force field based,GM map;density functional theory calculation based,GD map),and for the fast prediction of backbone amide-I vibrational frequency.The advantages and disadvantages of two maps based on different theories were systematically demonstrated,and the maps' performance in interpreting the amide-I spectra of ?-peptides were also evaluated.These results suggest that GM map is easier to construct and the obtained amide-I vibrational frequencies reproduce experimental datas satisfactorily,while GD map brings insights into the electronic structures of NEPA and its chemical environment.2.Structural and spectroscopic features of a model dipeptide(glycine dipeptide,GLYD)in the gas phase and in aqueous solution were systematically investigated.The electrostatic potential from the solvent molecules was calculated and projected onto the backbone of GLYD,and transformed to the amide-I frequency difference for GLYD in gas phase and solution phase.The secondary structure dependent amide-I frequency in gas phase was also introduced for the consideration of the possible vibrational coupling that was intrinsically included in GLYD conformers.An electrostatic frequency map with secondary structural sensitivity was then built for the fast and accurate vibrational frequency prediction of the amide-I band for GLYD in solution.3.The electrostatic potentials on the amide units of dipeptide originated from dipeptide backbone and heavy water were calculated and related to the amide-I frequency difference for dipeptide in gas phase and solution phase,together with the secondary structure dependent amide-I frequency in gas phase obtained by DFT calculations,the electrostatic frequency maps were parameterized for seven dipeptides with secondary structural sensitivity,respectively.These maps are helpful for understanding amide-I vibrational spectra of dipeptide.The instantaneous structures selected from MD trajectories of each dipeptide were sampled for a hybrid map construction.The map parameters were applied for each amide unit of A?25-35 polypeptide,respectively.The distributions of refined amide-I vibrational frequency of this polypeptide in heavy water reasonably predict its amide-I vibrational spectrum.This results suggest that these parameters are able to reveal different structure and chemical environment around different amide units of this polypeptide.4.With the help of metadynamic and adaptive biasing force,the enhanced sampling molecular simulations were performed for A?25-35 monomer,dimer,and their azido-modification derivatives in solution.The conformational statistic analysis was performed for this polypeptide and its azido-modification derivatives,the free energy landscapes in selected coordinate space were also obtained,their structural tendencies were revealed.The results suggest that the formation of ?-sheet is restrained by the introduction of azido group into the middle residue of A?25-35 and the population of?-helix structure increases.