The amide III region of the peptide infrared and Raman spectra has been used to determine the relative populations of the three major backbone conformations (PII, ß, and alphaR) in 19 amino acid dipeptides. The results provide a benchmark for force field or other methods of predicting backbone conformations in flexible peptides. There are three resolvable backbone bands in the amide III region. The major population is either PII or ß for all dipeptides except Gly, whereas the αlphaR population is measurable but always minor (( 10%) for 18 dipeptides. (The Gly φ,ψ map is complex and so is the interpretation of the amide III bands of Gly.) There are substantial differences in the relative ß and PII populations among the 19 dipeptides. Theband frequencies have been assigned as PII, 1317-1306 cm-1; αlphaR, 1304-1294 cm-1; and ß, 1294-1270 cm-1. The three bands were measured by both attenuated total reflection spectroscopy and by Raman spectroscopy. Consistent results, both for band frequency and relative population, were obtained by both spectroscopic methods. The ß and PII bands were assigned from the dependence of the 3J(HN,Hα) coupling constant (known for all 19 dipeptides) on the relative ß population. The PII band assignment agrees with one made earlier from Raman optical activity data. The temperature dependencesof the relative ß and PII populations fit the standard model with Boltzmann-weighted energies for alanine and leucine between 30 and 60°C.
COBISS.SI-ID: 4611098
Recent calorimetric measurements of the solvation enthalpies of some dipeptide analogs confirm our earlier prediction that the principle of group additivity is not valid for the interaction of the peptide group with water. We examine the consequences for understanding the properties of peptide solvation. A major consequence is that the current value of the peptide solvation enthalpy, which is a basic parameter in analyzing the energetics of protein folding, is seriously wrong. Electrostatic calculations of solvation free energies provide an estimate of the size and nature of the error.
COBISS.SI-ID: 4103962
The hydrophobic effect (HE) is commonly associated with the demixing of oil and water at ambient conditions and plays the leading role in determining the structure and stability of biomolecular assembly in aqueous solutions. On the molecular scale HE has an entropic origin. It is believed that hydrophobic particles induce order in the surrounding water by reducing the volume of configuration space available for hydrogen bonding. Here we show with computer simulation results that this traditional picture, based on average structural features of hydration water, configurational properties of single water molecules, and up to pairwise correlations, is not correct. Analyzing collective fluctuations in water clusters we are able to provide a fundamentally new picture of HE based on pronounced many-body correlations affecting the switching of hydrogen bonds (HBs) between molecules. These correlations emerge as a nonlocal compensation of reduced fluctuations of local electrostatic fields in the presence of an apolar solute. We propose an alternative view which may also be formulated as a maximization principle: The electrostatic noise acting on water molecules is maximized under the constraint that each water molecule on average maintains as many HBs as possible. In the presence of the solute the maximized electrostatic noise is a result of nonlocal fluctuations in the labile HB network giving rise to strong correlations among at least up to four water molecules.
COBISS.SI-ID: 5094426
The interaction between two associating hydrophobic particles has traditionally been explained in terms of the release of entropically frustrated hydration shell water molecules. However, this picture cannot account for the kinetics of hydrophobic association and is therefore not capable of providing a microscopic description of the hydrophobic interaction (HI). Here, Monte Carlo simulations of a pair of molecular-scale apolar solutes in aqueous solution reveal the critical role of collective fluctuations in the hydrogen bond (HB) network for the microscopic picture of the HI. The main contribution to the HI is the relaxation of solute-water translational correlations. The existence of a heat capacity maximum at the desolvation barrier is shown to arise from softening of non-HB water fluctuations and the relaxation of many-body correlations in the labile HB network. The microscopic event governing the kinetics of hydrophobic association has turned out to be a relatively large critical collective fluctuation in hydration water displacing a substantial fraction of HB clusters from the inner to the outer region of the first hydration shell.
COBISS.SI-ID: 36953605
The binding mode of naphthalene-N-sulfonyl-D-glutamic acid derivatives, novel MurD ligase inhibitors was determined using a combination of NMR methods and theoretical simulations of molecular dynamics. Mur ligases are recently discovered intracellular bacterial enzymes that are involved in the peptidoglycan biosynthetic pathway in bacterial cells and are therefore attractive protein targets for development of novel antimicrobial agents. Despite several attempts there are still no satisfactory results regarding the development of novel antibacterial drugs with potent inhibitor activity against Mur ligases. This is a consequence of insufficient effectiveness of drug design methodologies. Too much expectation has been placed on rigid molecular structures determined by X-ray diffraction. Therefore the studies of dynamical and structural aspect of binding mode of novel Mur ligases inhibitors are necessary. In our studies the conformational flexibility of bound inhibitors was identified by NMR experiments and further examined by unrestrained molecular dynamic simulations. The results revealed the differing degrees of inhibitor flexibility and their effect on particular inhibitor-receptor contacts. The degree of conformational flexibility depends on the specificity of the inhibitor molecular structure and adaptability within the binding site and can be related to the differences in the activity of novel inhibitors. The importance of hydrophobic inhibitor-receptor interactions for increased inhibitory activity of novel ligands was specified and the segments of molecular structure that are responsible for them were identified. The guidelines for the design of more active analogues were given.
COBISS.SI-ID: 4121626