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QM/MM Study (mm + study)
Selected AbstractsDFT/MM Study on Copper-Catalyzed Cyclopropanation , Enantioselectivity with No Enthalpy BarrierEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 33 2008Galí Drudis-Solé Abstract The enantioselectivity in the reaction of [Cu(adam-box)(CHCO2Me)] {adam-box = 2,2,-isopropylidenebis[(4R)-(1-adamantyl)-2-oxazoline]} with Ph2C=CH2 was analyzed computationally by ONIOM(B3LYP:UFF) calculations. The lack of transition states in the potential-energy surface precludes the use of conventional approaches and requires the definition of reaction paths in an approximate Gibbs free-energy surface. The procedure is time consuming and intrinsically less accurate than the usual approaches based on enthalpic energy surfaces, but it produces results in reasonable agreement with experiment, which furthermore allow identification of the key interactions responsible for chiral discrimination.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] A QM/MM Study of Cisplatin,DNA Oligonucleotides: From Simple Models to Realistic SystemsCHEMISTRY - A EUROPEAN JOURNAL, Issue 22 2006Arturo Robertazzi Abstract QM/MM calculations were employed to investigate the role of hydrogen bonding and , stacking in several single- and double-stranded cisplatin,DNA structures. Computed geometrical parameters reproduce experimental structures of cisplatin and its complex with guanine,phosphate,guanine. Following QM/MM optimisation, single-point DFT calculations allowed estimation of intermolecular forces through atoms in molecules (AIM) analysis. Binding energies of platinated single-strand DNA qualitatively agree with myriad experimental and theoretical studies showing that complexes of guanine are stronger than those of adenine. The topology of all studied complexes confirms that platination strongly affects the stability of both single- and double-stranded DNAs: PtNH,,,X (X = N or O) interactions are ubiquitous in these complexes and account for over 70,% of all H-bonding interactions. The , stacking is greatly reduced by both mono- and bifunctional complexation: the former causes a loss of about 3,4 kcal,mol,1, whereas the latter leads to more drastic disruption. The effect of platination on Watson,Crick GC is similar to that found in previous studies: major redistribution of energy occurs, but the overall stability is barely affected. The BH&H/AMBER/AIM approach was also used to study platination of a double-stranded DNA octamer d(CCTG*G*TCC),d(GGACCAGG), for which an experimental structure is available. Comparison between theory and experiment is satisfactory, and also reproduces previous DFT-based studies of analogous structures. The effect of platination is similar to that seen in model systems, although the effect on GC pairing was more pronounced. These calculations also reveal weaker, secondary interactions of the form Pt,,,O and Pt,,,N, detected in several single- and double-stranded DNA. [source] [Fe-Fe]-hydrogenase reactivated by residue mutations as bridging carbonyl rearranges: A QM/MM studyINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 14 2010Stefan Motiu Abstract In this work, we found aqueous enzyme phase reaction pathways for the reactivation of the exogenously inhibited [Fe-Fe]-hydrogenases by O2, or OH,, which metabolizes to H2O (Dogaru et al., Int J Quantum Chem 2008, 108; Motiu et al., Int J Quantum Chem 2007, 107, 1248). We used the hybrid quantum mechanics/molecular mechanics (QM/MM) method to study the reactivation pathways of the exogenously inhibited enzyme matrix. The ONIOM calculations performed on the enzyme agree with experimental results (Liu et al., J Am Chem Soc 2002, 124, 5175), that is, wild-type [Fe-Fe]-hydrogenase H-cluster is inhibited by oxygen metabolites. An enzyme spherical region with a radius of 8 Ĺ (from the distal iron, Fed) has been screened for residues that prevent H2O from leaving the catalytic site and reactivate the [Fe-Fe]-hydrogenase H-cluster. In the screening process, polar residues were removed, one at a time, and frequency calculations provided the change in the Gibbs' energy for the dissociation of water (due to their deletion). When residue deletion resulted in significant Gibbs' energy decrease, further residue substitutions have been carried out. Following each substitution, geometry optimization and frequency calculations have been performed to assess the change in the Gibbs' energy for the elimination of H2O. Favorable thermodynamic results have been obtained for both single residue removal (,G,Glu374 = ,1.6 kcal/mol), single substitution (,GGlu374His = ,3.1 kcal/mol), and combined residue substitutions (,GArg111Glu;Thr145Val;Glu374His;Tyr375Phe = ,7.5 kcal/mol). Because the wild-type enzyme has only an endergonic step to overcome, that is, for H2O removal, by eliminating several residues, one at a time, the endergonic step was made to proceed spontaneously. Thus, the most promising residue deletions which enhance H2O elimination are ,Arg111, ,Thr145, ,Ser177, ,Glu240, ,Glu374, and ,Tyr375. The thermodynamics and electronic structure analyses show that the bridging carbonyl (COb) of the H-cluster plays a concomitant role in the enzyme inhibition/reactivation. In gas phase, COb shifts towards Fed to compensate for the electron density donated to oxygen upon the elimination of H2O. However, this is not possible in the wild-type enzyme because the protein matrix hinders the displacement of COb towards Fed, which leads to enzyme inhibition. Nevertheless, enzyme reactivation can be achieved by means of appropriate amino acid substitutions. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010 [source] Ab initio QM/MM study of excited state electron transfer between pyrene and 4,4,-bis(dimethylamino)-diphenylmethane with different solvent systems: Role of hydrogen bonding within solvent moleculesINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 4 2005Kakali Sen Abstract The exciplex is a charge transfer species formed in the process of electron transfer between an electron donor and an electron acceptor and hence is very sensitive to solvent polarity. In order to understand the role of solvent in exciplex formation between pyrene (PY) and 4,4,-bis(dimethylamino)diphenylmethane (DMDPM), we used two types of solvent approximations: an implicit solvent model and an explicit solvent model. The difference in energies between the excited and the meta-stable Frank,Condon state (,E) of the structures were assumed to correspond to the emission maximum of the exciplex in different solvents. The ,E values show the trend of stabilization of the exciplex with an increase in solvent polarity. This trend in stabilization is substantially more prominent in the explicit solvent model than that with the implicit solvent model. The ,E value obtained in methanol reflects equal stabilization compared to that in a more polar solvent, N,N-dimethylformamide. This extra stabilization of the exciplex may be explained on the basis of the H-bonding capability of the protic solvent, methanol. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005 [source] Force-field parameters for the simulation of tetrahedral intermediates of serine hydrolasesJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 1 2009Nikolaj Otte Abstract CHARMM force-field parameters are reported for the tetrahedral intermediate of serine hydrolases. The fitting follows the standard protocol proposed for CHARMM22. The reference data include ab initio (RHF/6-31G*) interaction energies of complexes between water and the model compound 1,1-dimethoxyethoxide, torsional profiles of related model compounds from correlated ab initio (MP2/6-311+G*//B3LYP/6-31+G*) calculations, as well as molecular geometries and vibrational frequencies from density functional theory (B3LYP/6-31+G*). The optimized parameters reproduce the target data well. Their utility is demonstrated by a QM/MM study of the tetrahedral intermediate in Bacillus subtilis lipase A, and by classical molecular modeling of enantioselectivity in Pseudomonas aeruginosa lipase and its mutants. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009 [source] | ||||||||||