Glycoside hydrolases (GH) bind tightly to the sugar moiety at glycosidic bond being hydrolyzed stabilize its transition state conformation. We endeavored assess importance of glucose-binding residues in GH family 116 (GH116) β-glucosidases, which include human β-glucosylceramidase 2 (GBA2), by mutagenesis followed kinetic characterization, X-ray crystallography, and ONIOM calculations on Thermo...

objective(s): the novel 7-hydroxycoumarinyl gallates derivatives are detected in many pharmaceutical compounds like anticancer and antimicrobial agents. whereas carbon nanotubes (cnts) have been discussed for nanomedicine applications and in particular as drug delivery systems. the capability of armchair (5, 5) swcnt -based drug delivery system in the therapy of anticancer has been investigated...

Two oligomers, each containing 3 l-lysine residues, were used as model molecules for the simulation of the beta-sheet conformation of varepsilon-polylysine (varepsilon-PLL) chains. Their C terminals were capped with ethylamine and N terminals were capped with alpha-l-aminobutanoic acid, respectively. The calculations were carried out with the hybrid two-level ONOIM (B3LYP/6-31G:PM3) computation...

Nicotinamidase (Nic) is a key zinc-dependent enzyme in NAD metabolism that catalyzes the hydrolysis of nicotinamide to give nicotinic acid. A multi-scale computational approach has been used to investigate the catalytic mechanism, substrate binding and roles of active site residues of Nic from Streptococcus pneumoniae (SpNic). In particular, density functional theory (DFT), molecular dynamics (...

The first example of intramolecular nucleophilic addition of an alcohol to a fullerene double bond is described. In particular, the straightforward one-step reaction of commercially available sarcosine, hydroxyacetaldehyde, and [60]fullerene, in refluxing chlorobenzene, affords a structurally complex novel pyrrolidinofullerene endowed with a furan ring simultaneously fused to both the pyrrolidi...

Different deprotonation paths of the radical cation formed by one-electron oxidation of 2'-deoxyguanosine (2dG) sites in DNA have been studied using Density Functional Theory (M05-2X/6-31+G(d,p)) and ONIOM methodology (M05-2X/6-31+G(d,p):PM6) in conjunction with the SMD model to include the solvent effects. Models of increased complexity have been used ranging from the isolated nucleoside to a ...

The combination of theoretical models of macromolecules that exist at different spatial and temporal scales has become increasingly important for addressing complex biochemical problems. This work describes the extension of concurrent multiscale approaches, introduces a general framework for carrying out calculations, and describes its implementation into the CHARMM macromolecular modeling pack...

We present ONIOM calculations using density functional theory (DFT) as the high and AM1 as the medium level that explore the abilities of different hexapeptide sequences to terminate the growth of a model for the tau-amyloid implicated in Alzheimer's disease. We delineate and explore several design principles (H-bonding in the side chains, using antiparallel interactions on the growing edge of ...

We recently reported crystallographic evidence that the hydrogen bonds which can stabilize oxygen-centered negative charge within enzyme oxyanion holes are rarely found in the place they should be expected on the basis of the analysis of small-molecule crystal structures. We investigated this phenomenon using calculations on simplified active site models. A recent paper suggested that several a...