Studies On The Weak Interactions Of Biochemical Model Molecules And Small Biomolecules In Aqueous Solution

Weak interaction plays an essential role in the structures and properties of proteins and nucleic acids as well as in the behavior of many biological systems. In the present work, NMR, FTIR and computer simulations are combined to investigate the weak interactions in the biochemical model molecules and small biomolecules systems.N-methylacetamide (NMA), one of the simplest model molecules of peptide group, has been deeply studied. The chemical association theory is established to describe the NMR chemical shifts and thermodynamic behavior. Furthermore, IR spectra and density functional theory have been performed to study the structures and interactions in NMA-water mixtures. The changes in bond length and frequency shift of the structures give good reasons for the red shift and blue shift, which represents excellent agreement with the IR experiment. In addition, all atom simualtions and NMR experiment are adopted to study the mixture. And the two methyl groups in NMA molecule are found to show different capabilities in forming weak C-H…O contacts in the mixtures from the radial distribution functions (RDFs). The temperature-dependent NMR results of the different methyl groups also show excellent agreements with the MD simulations.In order to obtain deeper insight on the amide-water system, the MD simulations and the temperature-dependent NMR are used to study the N,N-Dimethylformamide (DMF) and N,N-Dimethylacetamide (DMA) aqueous solution. The weak interactions in the amide-water systems are revealed by the hydrogen-bonding network in MD simulations and NMR spectrum. In addition, η_rel^E and η_rel^HB are introduced todescribe the anomalous non-ideal behaviors of amide-water mixtures. The simulation is compared with excess enthalpy of mixing, which shows good concentration dependences.All-atom MD simulations and NMR spectra are successful in revealing the structures and interactions in the amide-water mixtures, and those methods are further used to study the glutathione (GSH) in aqueous solution.The nature tripeptide glutathione plays an essential role in the structures and properties of proteins andnucleic acids as well as in the behavior of many solvent systems. The GSH is flexible in the aqueous solution. The average structure appears to be the extended conformation. The RDF and the temperature-dependent NMR also show that the different hydrogen atoms in the cysteine (Cys) and glycin (Gly) display the different capability in forming the hydrogen bonds. In addition, the weak interactions of GSH in DMSO solution are further investigated to compare with those interactions of GSH in aqueous solution. And the different roles are found in the DMSO and aqueous solution. The conformations of GSH are more flexible in the aqueous solution than those in DMSO, which denote that the aqueous solution has the special properties. Those varieties of the conformation and the clusters will affect the properties of the GSH in solution.All in all, the experiment, chemical theory and computer simulations are combined to investigate the biochemical model molecules and small biomolecules in solution. The frame of studies on weak interactions is established to successfully reveal the structures and interactions in the systems. We expect that these methods are applicable to investigate more important phenomena in biochemistry.