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
Dipeptides are amino acids blocked with an acetyl and an N-methyl group. The amino acids in dipeptides have structural properties similar to amino acid residues in proteins; this is why structures of dipeptides are important for understanding structures of proteins. We have determined the dipeptide structures of 19 basic amino acids in a water solution. Using spectroscopic methods, we have demonstrated the presence of three conformations of dipeptides in water: the PII, β, and the αR. The proportion of the αR conformation in all dipeptides is surprisingly low (( 10%).
COBISS.SI-ID: 4611098
The NMR studies and molecular dynamics simulations of ligand-MurD complexes have been performed to obtain the insight into dynamic properties of novel complexes, which can significantly upgrade the drug design studies that are based solely on the static crystal structures. The results revealed the differing degrees of ligand flexibility and their effect on particular ligand-enzyme contacts. The degree of conformational flexibility depends on the specificity of the ligand molecular structure and can be related to the differences in their inhibitory activities.
COBISS.SI-ID: 4121626
One of the most difficult problems in chemistry is how a protein molecule folds from an unfolded state to its native conformation. It has been suggested that the local structural order (i.e., residual structure) may guide a polypeptide chain from the denatured to the native state. To understand the process of protein folding and misfolding, it is important to understand the nature of the local structural order in unfolded peptides and proteins. The local structural order in unfolded proteins is demonstrated by the following four indicators: the backbone conformational preferences, the nearest-neighbor effect, the cooperative formation of larger local structures, and the hydrophobic clusters. These indicators differ in the level of cooperativity, that is, the number of adjacent residues involved. The physical background of the local structural order in unfolded polypeptides is a highly controversial issue. In this review we show that solvation and electrostatic interactions can quantitatively explain the behavior of unfolded peptides and proteins.
COBISS.SI-ID: 5044250
We employed DFT calculations to investigate the nature of the binding between the physiological form of glutathione (GSH) and cadmium dication (Cd2+) in aqueous solution. Glutathione is a ubiquitous tripeptide, γ-L-glutamyl-L-cysteinyl-glycine, which plays a number of vital roles in cell metabolism. The results revealed that, upon complexation, the cysteine –SH group gets deprotonated by the proton transfer to the neighbouring glycine carboxylic group, facilitated by the formation of favourable Cd2+...S– coordination, which lowers cysteine pKa(SH) value by around 13 pKa units. This produces adduct in which GSH interacts with Cd2+ predominantly through the cysteine thiolate anion and the ionized glutamine carboxylic group. The transferring proton reverts glycine –COO– group to its neutral trans –COOH form, which gets stabilized by OH...S– hydrogen bonding. We found our results to be fully consistent with vibrational and NMR spectroscopic measurements.
COBISS.SI-ID: 5157914