How a crosslinker agent interacts with the ß-glucosidase enzyme surface in an aqueous solution: Insight from quantum mechanics calculations and molecular dynamics simulations.

In this study, surficial interactions of glutaraldehyde (GA) as an important crosslinker agent with the ß-glucosidase (BGL) enzyme surface were investigated by theoretical methods. Since the inherent constraints of experimental methods limit their application to find the molecular perspective of these significant interactions in enzyme immobilization, theoretical methods were used as a complementary tool to understand this concept. The Minnesota density functional calculations showed that the chair conformations of the oxane-2,6-diol form of the GA were more stable than its free aldehyde form. MD simulations of propylamine-GA molecules, as a representative of attached-GA, in aqueous solutions of different concentrations were done to determine the molecular basis of surficial interactions with the BGL surface. The root mean square fluctuation (RMSF) demonstrated that the maximum flexibility of the BGL enzyme belonged to 460-480 residues in all solutions. Based on the spatial distribution function (SDF) analysis, the active site entrance was the most favored region to accumulate solute molecules. Radial distribution function (RDF) results showed that all forms of propylamine-GA molecules interacted from their head side with the lysine residues of BGL, which Lys247, Lys376, and Lys384 were found to be the most interactive lysine residues. Also, hydrogen bond (HB) analysis from two viewpoints confirmed HB formation possibility between propylamine-GA molecules and these lysine residues. These results explained which regions of the BGL have the maximum possibility to interact and link to GA and help us in understanding the process of enzyme immobilization.

The effects of fluorine substitution on the chemical properties and inhibitory capacity of Donepezil anti-Alzheimer drug; density functional theory and molecular docking calculations.

Drug fluorination has the potential to reproduce useful drugs with decreasing the side effect of them. Identifying the effect of this improvement on the chemical properties and biological interactions of drug symbolizes a meaningful progress in drug design. Here the fluorination of Donepezil as an anti-Alzheimer drug, including 7 fluorinated derivatives of it, was investigated computationally. In the first part of our calculations, the most important chemical properties of drug that affects the drug efficiency were investigated by applying the M06/6-31g (d, p) and M062X/6-31g (d, p) levels of theories. Findings showed that the fluorine substitution changed the drug stability as altered the solubility and molecular polarity. Furthermore, the intramolecular hydrogen bonding, charge distribution and electron delocalization of the drug were affected by this replacement. In the second section, the effect of fluorination on the drug⋯enzyme interactions was evaluated by using two effective methods Based on the molecular docking and density functional theory (DFT) calculations fluorine substitution influenced the Donepezil⋯Acetylcholinesterase interactions. Calculated binding energies by two computational methods displayed that the fluorine replacement changed the binding affinity of drug. Finally, the most significant non-bonded interactions between drugs and involved residues were investigated by bond length data analysis.

Configurational study of amino-functionalized silica surfaces: A density functional theory modeling.

Despite extensive studies of the amino-functionalized silica surfaces, a comprehensive investigation of the effects of configuration and hydrolysis of 3-aminopropyltriethoxysilan (APTES) molecules attached on silica has not been studied yet. Therefore, the methods of quantum mechanics were used for the study of configuration and hydrolysis forms of APTES molecules attached on the surface. For this purpose, five different categories based on the number of hydrolyzed ethoxy groups including 16 configurations were designed and analyzed by the density functional theory (DFT) method. The steric hindrance as an effective factor on the stability order was extracted from structural analysis. Other impressive parameters such as the effects of hydrogen bond and electron delocalization energy were obtained by using the atoms in molecules (AIM) and natural bond orbitals (NBO) theories. Consequently, it was found that the stability of configurations was attributed to steric effects, hydrogen bond numbers and electron delocalization energy. The maximum stability was achieved when at least two of these parameters cooperate with each other.

Theoretical studies on the deacylation step of acylated Candida Antarctica lipase B: structural and reaction pathway analysis.

The deacylation step of acylated Candida Antarctica lipase B, which was acylated with methylcaprylate (MEC) and acetylcholine (ACh), has been studied by using density functional theory method. Free energies of the entire reaction were calculated for enzyme deacylation by water and hydrogen peroxide that represented hydrolysis and perhydrolysis reactions, respectively. The calculations displayed that a stepwise mechanism there was with the enzyme-product complex being a deep minimum on the free energy surfaces of both of two reactions. The tetrahedral intermediate formation was the rate-determining step of all reactions, which needed 8.1 to 10.5kcalmol(-1) for activation in different reactions. In the second stage of the reaction, fewer free energy barriers, between 4.7 and 5.9kcalmol(-1), were identified to enable the proton transfer from His224 to Ser105 and the breakdown of the tetrahedral intermediate. These calculated activation free energies approved theoretical possibility of both of two reactions for two substrates. Finally, an applied tool examined the interactions role in the stability and energy levels of different chemical species.