The octanol-water partition coefficient is an important physical-chemical characteristic widely used to describe hydrophobic/hydrophilic properties of chemical compounds. The partition coefficient is related to the transfer free energy of a compound from water to octanol. Here, we introduce a new protocol for prediction of the partition coefficient based on the statistical-mechanical, 3D-RISM-KH molecular theory of solvation. It was shown recently that with the compound-solvent correlation functions obtained from the 3D-RISM-KH molecular theory of solvation, the free energy functional supplemented with the correction linearly related to the partial molar volume obtained from the Kirkwood-Buff/3D-RISM theory, also called the "universal correction" (UC), provides accurate prediction of the hydration free energy of small compounds, compared to explicit solvent molecular dynamics [ Palmer , D. S. ; J. Phys.: Condens. Matter 2010 , 22 , 492101 ]. Here we report that with the UC reparametrized accordingly this theory also provides an excellent agreement with the experimental data for the solvation free energy in nonpolar solvent (1-octanol) and so accurately predicts the octanol-water partition coefficient. The performance of the Kovalenko-Hirata (KH) and Gaussian fluctuation (GF) functionals of the solvation free energy, with and without UC, is tested on a large library of small compounds with diverse functional groups. The best agreement with the experimental data for octanol-water partition coefficients is obtained with the KH-UC solvation free energy functional.

Vous avez des questions? Nous pouvons vous aider. Pour communiquer directement avec un auteur, consultez la première page de la revue dans laquelle son article a été publié afin de trouver ses coordonnées. Si vous n'arrivez pas à les repérer, communiquez avec nous à PublicationsArchive-ArchivesPublications@nrc-cnrc.gc.ca. Questions? Contact the NRC Publications Archive team atPublicationsArchive-ArchivesPublications@nrc-cnrc.gc.ca. If you wish to email the authors directly, please see the first page of the publication for their contact information. NRC Publications Archive Archives des publications du CNRCThis publication could be one of several versions: author's original, accepted manuscript or the publisher's version. / La version de cette publication peut être l'une des suivantes : la version prépublication de l'auteur, la version acceptée du manuscrit ou la version de l'éditeur. For the publisher's version, please access the DOI link below./ Pour consulter la version de l'éditeur, utilisez le lien DOI ci-dessous.http://doi.org/10.1021/jp507393uAccess and use of this website and the material on it are subject to the Terms and Conditions set forth at Molecule-surface recognition between heterocyclic aromatic compounds and kaolinite in toluene investigated by molecular theory of solvation and thermodynamic and kinetic experiments Huang, WenJuan; Dedzo, Gustave Kenne; Stoyanov, Stanislav R.; Lyubimova, Olga; Gusarov, Sergey; Singh, Shashank; Lao, Hayes; Kovalenko, Andriy; Detellier, Christian http://nparc.cisti-icist.nrc-cnrc.gc.ca/fra/droits L'accès à ce site Web et l'utilisation de son contenu sont assujettis aux conditions présentées dans le site LISEZ CES CONDITIONS ATTENTIVEMENT AVANT D'UTILISER CE SITE WEB. NRC Publications Record / Notice d'Archives des publications de CNRC:http://nparc.cisti-icist.nrc-cnrc.gc.ca/eng/view/object/?id=7b90aae5-5f3a-4009-aa11-d27eb5d6926a http://nparc.cisti-icist.nrc-cnrc.gc.ca/fra/voir/objet/?id=7b90aae5-5f3a-4009-aa11-d27eb5d6926a ABSTRACT: Molecular recognition interactions between kaolinite and a series of heterocyclic aromatic compounds (HAC) representative of the N-and S-containing moieties in petroleum asphaltene macromolecules are investigated using the threedimensional reference interaction site model with the Kovalenko−Hirata closure approximation (3D-RISM-KH) theory of solvation and experimental techniques in toluene solvent. The statistical-mechanical 3D-RISM-KH molecular theory of solvation predicts the adsorption configuration and thermodynamics from the 3D site density distribution functions and total solvation free energy, respectively, for adsorption of HAC and toluene on kaolinite. Spectrophotometric measurements show that, among the HAC studied, only acridine and phenanthridine adsorb quantitatively on kaolinite. For these pyridinic HAC, the adsorption results fitted to the Langmuir isotherm in the monolayer domain suggest a uniform monolayer of HAC molecules. The 3D-RISM-KH studies predict that the aluminum hydroxide surface of kaolinite is preferred for...

Density functional theory-based methods in combination with large chemical models have been used to investigate the mechanism of the second half-reaction catalyzed by Thr-tRNA synthetase; aminoacyl transfer from Thr-AMP onto the A763'OH of the cognate tRNA. In particular, we have examined pathways in which an active site His309 residue is either protonated or neutral (i.e., potentially able to act as a base). In the protonated His309-assisted mechanism, the rate-limiting step is formation of the tetrahedral intermediate. The barrier for this step is 155.0 kJ mol−1 and thus, such a pathway is concluded to not be enzymatically feasible. For the neutral His309-assisted mechanism two models were used with the difference being whether Lys465 was included. For either model the barrier of the rate-limiting step is below the upper-thermodynamic enzymatic limit of ∼125 kJ mol−1. Specifically, without Lys465 the rate-limiting barrier is 122.1 kJ mol−1 and corresponds to a rotation about the tetrahedral intermediates Ccarb—OH bond. For the model with Lys465 the rate-limiting barrier is slightly lower and corresponds to the formation of the tetrahedral intermediate. Importantly, for both neutral His309’ models the neutral amino group of the threonyl substrate directly acts as the proton accepter; in the formation of the tetrahedral intermediate the A763'OH proton is directly transferred onto the Thr-NH2. Therefore, the overall mechanism follows a general substrate assisted catalytic mechanism.

UDP-galactopyranose mutase (UGM) is a key flavoenzyme involved in cell wall biosynthesis of a variety of pathogenic bacteria and hence, integral to their survival. It catalyzes the interconversion of UDP-galactopyranose (UDP-Galp) and UDP-galactofuranose (UDP-Galf); interconversion of the galactose moieties six- and five-membered ring forms. We have synergistically applied both density functional theory (DFT)-cluster and ONIOM quantum mechanics/molecular mechanics (QM/MM) hybrid calculations to elucidate the mechanism of this important enzyme and to provide insight into its uncommon mechanism. It is shown that the flavin must initially be in its fully reduced form. Furthermore, it requires an N5(FAD)-H proton, which, through a series of tautomerizations, is transferred onto the ring oxygen of the substrate's Galp moiety to facilitate ring-opening with concomitant Schiff base formation. Conversely, Galf formation is achieved via a series of tautomerizations involving proton transfer from the galactose's -O4(Gal)H group ultimately onto the flavin's N5(FAD) center. With the DFT-cluster model, the overall rate-limiting step with a barrier of 120.0 kJ mol(-1) is the interconversion of two Galf-flavin tautomers: one containing a C4(FAD)-OH group and the other a tetrahedral protonated-N5(FAD) center. In contrast, in the QM/MM model a considerably more extensive chemical model was used that included all of the residues surrounding the active site, and modeled both their steric and electrostatic effects. In this approach, the overall rate-limiting step with a barrier of 99.2 kJ mol(-1) occurs during conformational rearrangement of the Schiff base linear galactose-flavin complex. This appears due to the lack of suitable functional groups to facilitate the rearrangement.

The structure and nature of the fully bound active site of Threonyl-tRNA Synthetase (ThrRS) for the second half-reaction has been investigated using molecular dynamics simulations. More specifically, we examined the ThrRS active site with both the substrate Threonyl-AMP and the cosubstrate cognate Threonyl-tRNA bound. Furthermore, we also considered the cases in which an active-site histidyl residue (His309) is either neutral or protonated. Moreover, we considered the role a water molecule may play in formation of a viable Michaelis complex. From the results it is found that the most likely role of His309 is in binding and properly orientating the ribose of the Ado76 nucleotidyl residue of the threonyl-tRNA via formation of a direct His309···Ado76 hydrogen bond, i.e., without involvement of a water. In addition, the imidazole of the His309 residue is likely neutral. It was found that upon protonation the positioning of the Ado76-3'-OH was perturbed, leading to a reduced chance for nucleophilic attack of the threonyl's C1 center.

Glycosidic bonds are remarkably resistant to cleavage by chemical hydrolysis. Glycoside hydrolases catalyze their selective hydrolysis in oligosaccharides, polysaccharides, and glycoconjugates by following nonredox catalytic pathways or a net redox-neutral catalytic pathway using NAD(+) and divalent metal ions as cofactors. GlvA (6-phospho-alpha-glucosidase) is a glycosidase belonging to family GH4 and follows a regioselective redox-neutral mechanism of glycosidic-bond hydrolysis that favors alpha- over beta-glycosides. Its proposed catalytic mechanism can be divided into two half-reactions: the first one activates the glucopyranose ring by successively forming intermediates that are oxidized at the 3-, 2-, and 1-positions of the ring, which ultimately facilitate the heterolytic deglycosylation. The second half-reaction is essentially the reverse of the first half-reaction, beginning with the pyranose ring hydroxylation at the anomeric carbon, and it is followed by 3-reduction and regeneration of the active forms of the catalytic site and its cofactors. We investigated the NAD(+)-dependent redox mechanism of glycosidic bond hydrolysis as catalyzed by GlvA through the combined application of density functional theory and a self-consistent reaction field to a large active-site model obtained from the crystallographic structure of the enzyme, then we applied natural bond orbital and second-order perturbation analyses to monitor the electron flow and change in oxidation state on each atomic center along the reaction coordinate to rationalize the energetics and regioselectivity of this catalytic mechanism. We find that in GlvA, the redox catalytic mechanism of hydrolysis is driven by the gradual strengthening of the axial endo-anomeric component within the hexose ring along the reaction coordinate to facilitate the heterolytic dissociation of the axial C1-O bond. In addition, the combined influence of specific components of the generalized anomeric effect fully explains the regioselectivity observed in the catalytic activity of GlvA.

Vous avez des questions? Nous pouvons vous aider. Pour communiquer directement avec un auteur, consultez la première page de la revue dans laquelle son article a été publié afin de trouver ses coordonnées. Si vous n'arrivez pas à les repérer, communiquez avec nous à PublicationsArchive-ArchivesPublications@nrc-cnrc.gc.ca. Questions? Contact the NRC Publications Archive team atPublicationsArchive-ArchivesPublications@nrc-cnrc.gc.ca. If you wish to email the authors directly, please see the first page of the publication for their contact information. NRC Publications Archive Archives des publications du CNRCThis publication could be one of several versions: author's original, accepted manuscript or the publisher's version. / La version de cette publication peut être l'une des suivantes : la version prépublication de l'auteur, la version acceptée du manuscrit ou la version de l'éditeur. NRC Publications Record / Notice d'Archives des publications de CNRC:http://nparc.cisti-icist.nrc-cnrc.gc.ca/eng/view/object/?id=f8d89406-113d-481f-b97f-a9bc19e92c39 http://nparc.cisti-icist.nrc-cnrc.gc.ca/fra/voir/objet/?id=f8d89406-113d-481f-b97f-a9bc19e92c39 We provide the molecular details on the binding mode that was not previously observed in the Xray experiments. We show that this mode, which is defined by the fine balance between the protein−ligand direct interactions and solvation effects, can trigger the protein's domain motion resulting in the holo-closed structure of the maltose-binding protein with the maltotriose ligand in excellent agreement with the experimental data. We also discuss the role of water in blocking unfavorable binding sites and watermediated interactions contributing to the stability of observable binding modes of maltotriose.

Type-2 quorum sensing (QS-2) is a cell-cell signaling process known to be used by a number of pathogenic bacteria and to play important roles in their population growth and virulence. S-ribosyl homocysteinase (LuxS) is a key enzyme in the formation of the signaling molecule of QS-2, autoinducer II (AI-2). In this study, substrate (S-ribosylhomocysteine: SRH) binding and possible initial reaction steps of its catalytic mechanism leading to formation of a putative 2-keto-SRH intermediate have been examined. Specifically, docking and MD simulations were used to gain insights into the structure of the active-site-bound substrate complex. An ONIOM QM/MM hybrid method was then used to elucidate the mechanism of the first stage of the enzyme catalytic process. It is shown that the substrate may bind within the active site when its ribosyl moiety is in the α- (α-SRH) or β-furanose (β-SRH) configuration or as a linear aldose (linear-SRH). The α-SRH complex is preferred, lying 47.5 kJ mol(-1) lower in energy than the next lowest energy initial complex β-SRH. However, the MD and QM/MM calculations indicate that an active site water stably locates within the active site and that it can facilitate ring-opening of either α-SRH or β-furanose, leading to formation of a common active-site-bound 2-keto-SRH intermediate, without the need to pass through a linear aldose SRH configuration. Hence, regardless of the ribose's configuration within the bound SRH substrate, LuxS is able to catalyze the conversion of SRH to a common 2-keto-SRH intermediate.