Configurational entropy in protein-peptide binding: computational study of Tsg101 ubiquitin E2 variant domain with an HIV-derived PTAP nonapeptide.

Configurational entropy is thought to influence biomolecular processes, but there are still many open questions about this quantity, including its magnitude, its relationship to molecular structure, and the importance of correlation. The mutual information expansion (MIE) provides a novel and systematic approach to extracting configurational entropy changes due to correlated motions from molecular simulations. We present the first application of the MIE method to protein-ligand binding using multiple molecular dynamics simulations to study the association of the ubiquitin E2 variant domain of the protein Tsg101 and an HIV-derived nonapeptide.

Quantum Mechanics/Molecular Mechanics Calculations of the Vanadium Dependent Chloroperoxidase.

Large quantum mechanics/molecular mechanics (QM/MM) calculations are used to probe the resting and initial protonated states of the vanadium dependent chloroperoxidase from the pathogenic fungus Curvularia inaequalis. QSite was used to model 433 residues and 24 structural waters with molecular mechanics, while 8 active-site residues and the vanadate cofactor (161 atoms) were represented at the B3LYP/lacvp* level of theory. Our previous study of small model systems implied that the resting state of the enzyme contains a trigonal bipyramidal vanadate with one hydroxyl group in the equatorial plane and another in the axial position.

Quantum mechanical models of the resting state of the vanadium-dependent haloperoxidase.

Density functional theory has been used to investigate structural and electronic properties of complexes related to the resting form of the active site of vanadium haloperoxidase as a function of environment and protonation state. Results obtained by studying models of varying size and complexity highlight the influence of environment and protonation state on the structure and stability of the metal cofactor. The study shows that, in the trigonal bipyramidal active site, where one axial position is occupied by a key histidine, the trans position cannot contain a terminal oxo group.

Solution chemistry of copper(II)-gentamicin complexes: relevance to metal-related aminoglycoside toxicity.

The adverse effect to the inner ear of aminoglycosides, drugs widely administered for the treatment of serious infections, appears to result from the interaction of these drugs with Cu(II) or Fe(II)/Fe(III) ions. To understand more completely the metal-induced side effects of one such antibiotic, gentamicin, we studied copper(II) coordination to gentamicin C1a by potentiometry, UV-vis, CD, and EPR spectroscopies, and ESI mass spectrometry. Only monomeric complexes of the CuH(n)L stoichiometry, with n ranging from 3 to -2, were detected over the pH range of 4-12.