Network analysis of dynamically important residues in protein structures mediating ligand-binding conformational changes.

According to the generalized conformational selection model, ligand binding involves the co-existence of at least two conformers with different ligand-affinities in a dynamical equilibrium. Conformational transitions between them should be guaranteed by intramolecular vibrational dynamics associated to each conformation. These motions are, therefore, related to the biological function of a protein. Positions whose mutations are found to alter these vibrations the most can be defined as key positions, that is, dynamically important residues that mediate the ligand-binding conformational change. In a previous study, we have shown that these positions are evolutionarily conserved. They correspond to buried aliphatic residues mostly localized in regular structured regions of the protein like ß-sheets and α-helices. In the present paper, we perform a network analysis of these key positions for a large dataset of paired protein structures in the ligand-free and ligand-bound form. We observe that networks of interactions between these key positions present larger and more integrated networks with faster transmission of the information. Besides, networks of residues result that are robust to conformational changes. Our results reveal that the conformational diversity of proteins seems to be guaranteed by a network of strongly interconnected key positions rather than individual residues.

Some Clues about Enzymes from Psychrophilic Microorganisms.

Enzymes purified from psychrophilic microorganisms prove to be efficient catalysts at low temperatures and possess a great potential for biotechnological applications. The low-temperature catalytic activity has to come from specific structural fluctuations involving the active site region, however, the relationship between protein conformational stability and enzymatic activity is subtle. We provide a survey of the thermodynamic stability of globular proteins and their rationalization grounded in a theoretical approach devised by one of us. Furthermore, we provide a link between marginal conformational stability and protein flexibility grounded in the harmonic approximation of the vibrational degrees of freedom, emphasizing the occurrence of long-wavelength and excited vibrations in all globular proteins. Finally, we offer a close view of three enzymes: chloride-dependent α-amylase, citrate synthase, and ß-galactosidase.

Vibrational normal modes calculation in the crystalline state of methylated monosaccharides: Anomers of the methyl-D-glucopyranoside and methyl-D-xylopyranoside molecules.

A structural investigation of the organic molecules is being carried out using vibrational spectroscopy. In this study, normal co-ordinate calculations of anomers of the methyl-D-glucopyranoside and methyl-ß-D-xylopyranoside in the crystalline state have been performed using the modified Urey-Bradley-Shimanouchi force field (mUBSFF) combined with an intermolecular potential energy function. The latter includes Van der Waals interactions, electrostatic terms, and explicit hydrogen bond functions. The vibrational spectra of the compounds recorded in the crystalline state, in the 4000-500 cm(-1) spectral region for the IR spectra, and in the 4000-20 cm(-1) spectral range for the Raman spectra are presented. After their careful examination, several differences in the intensities and frequency shifts have been observed. The theoretical spectra have been obtained after a tedious refinement of the force constants. Thus, on the basis of the obtained potential distribution, each observed band in IR and in Raman has been assigned to a vibrational mode. The obtained results are indeed in agreement with those observed experimentally and thus confirm the previous assignments made for the methyl-α and ß-D-glucopyranoside, as well as for the methyl-ß-D-xylopyranoside.