38 research outputs found
MDcons: Intermolecular contact maps as a tool to analyze the interface of protein complexes from molecular dynamics trajectories
No full textBackground: Molecular Dynamics ( MD) simulations of protein complexes suffer from the lack of specific tools in the analysis step. Analyses of MD trajectories of protein complexes indeed generally rely on classical measures, such as the RMSD, RMSF and gyration radius, conceived and developed for single macromolecules. As a matter of fact, instead, researchers engaged in simulating the dynamics of a protein complex are mainly interested in characterizing the conservation/variation of its biological interface.
Results: On these bases, herein we propose a novel approach to the analysis of MD trajectories or other conformational ensembles of protein complexes, MDcons, which uses the conservation of inter-residue contacts at the interface as a measure of the similarity between different snapshots. A "consensus contact map" is also provided, where the conservation of the different contacts is drawn in a grey scale. Finally, the interface area of the complex is monitored during the simulations. To show its utility, we used this novel approach to study two protein-protein complexes with interfaces of comparable size and both dominated by hydrophilic interactions, but having binding affinities at the extremes of the experimental range. MDcons is demonstrated to be extremely useful to analyse the MD trajectories of the investigated complexes, adding important insight into the dynamic behavior of their biological interface.
Conclusions: MDcons specifically allows the user to highlight and characterize the dynamics of the interface in protein complexes and can thus be used as a complementary tool for the analysis of MD simulations of both experimental and predicted structures of protein complexes
Accuracy of the DLPNO-CCSD(T) method for non-covalent bond dissociation enthalpies from coinage metal cation complexes
No full textThe performance of the domain based local pair-natural orbital coupled-cluster (DLPNO-CCSD(T)) method has been tested to reproduce the experimental gas phase ligand dissociation enthalpy in a series of Cu+, Ag+ and Au+ complexes. For 33 Cu+ - non-covalent ligand dissociation enthalpies all-electron calculations with the same method result in MUE below 2.2 kcal/mol, although a MSE of 1.4 kcal/mol indicates systematic underestimation of the experimental values. Inclusion of scalar relativistic effects for Cu either via effective core potential (ECP) or Douglass-Kroll-Hess Hamiltonian, reduces the MUE below 1.7 kcal/mol and the MSE to -1.0 kcal/mol. For 24 Ag+ - non-covalent ligand dissociation enthalpies the DLPNO-CCSD(T) method results in a mean unsigned error (MUE) below 2.1 kcal/mol and vanishing mean signed error (MSE). For 15 Au+ - non-covalent ligand dissociation enthalpies the DLPNO-CCSD(T) methods provides larger MUE and MSE, equal to 3.2 and 1.7 kcal/mol, which might be related to poor precision of the experimental measurements. Overall, for the combined dataset of 72 coinage metal ion complexes DLPNO-CCSD(T) results in a MUE below 2.2 kcal/mol and an almost vanishing MSE. As for a comparison with computationally cheaper density functional theory (DFT) methods, the routinely used M06 functional results in MUE and MSE equal to 3.6 and -1.7 kca/mol. Results converge already at CC-PVTZ quality basis set, making highly accurate DLPNO-CCSD(T) estimates to be affordable for routine calculations (single-point) on large transition metal complexes of > 100 atoms
Chermak-Delgado Simple Groups
No full textThis paper provides the first steps in classifying the finite solvable groups
having Property A, which is a property involving abelian normal subgroups. We
see that this classification is reduced to classifying the solvable
Chermak-Delgado simple groups, which the author defines. The author completes a
classification of Chermak-Delgado simple groups under certain restrictions on
the primes involved in the group order
Analysis and ranking of protein-protein docking models using inter-residue contacts and inter-molecular contact maps
No full textIn view of the increasing interest both in inhibitors of protein-protein interactions and in protein drugs themselves, analysis of the three-dimensional structure of protein-protein complexes is assuming greater relevance in drug design. In the many cases where an experimental structure is not available, protein-protein docking becomes the method of choice for predicting the arrangement of the complex. However, reliably scoring protein-protein docking poses is still an unsolved problem. As a consequence, the screening of many docking models is usually required in the analysis step, to possibly single out the correct ones. Here, making use of exemplary cases, we review our recently introduced methods for the analysis of protein complex structures and for the scoring of protein docking poses, based on the use of inter-residue contacts and their visualization in inter-molecular contact maps. We also show that the ensemble of tools we developed can be used in the context of rational drug design targeting protein-protein interactions
CONSRANK: a server for the analysis, comparison and ranking of docking models based on inter-residue contacts
No full textBioinformatics first published online December 21, 2014 (pagine non ancora attribuibili, saranno attribuite quando stampato
Troubles in the systematic prediction of transition metal thermochemistry with contemporary out-of-the-box methods
No full textThe recently developed DLPNO-CCSD(T) method and 7 popular DFT functionals (B3LYP, M06, M06L, PBE, PBE0, TPSS and TPSSh) with and without an empirical dispersion term have been tested to reproduce 111 gas phase reaction enthalpies involving 11 different transition metals. Our calculations, corrected for both relativistic effects and basis set incompleteness, indicate that most of the methods applied with default settings perform with acceptable accuracy on average. Nevertheless, our calculations also evidenced unexpected and non systematic large deviations for specific cases. For group 12 metals (Zn, Cd, Hg) most of the methods provided mean unsigned errors (MUE) less than 5.0 kcal/mol, with DLPNO-CCSD(T) and PBE methods performing excellently (MUE lower 2.0 kcal/mol). Problems started with group 4 metals (Ti and Zr). Best performer for Zr complexes with a MUE of 1.8 kcal/mol, PBE0-D3, provides a MUE larger than 8 kcal/mol for Ti. DLPNO-CCSD(T) provides a reasonable MUE of 3.3 kcal/mol for Ti reactions, but gives MUE a larger than 14.4 kcal/mol for Zr complexes, with all the larger deviations for reactions involving ZrF4. Large and non-systematic errors have been obtained for group 6 metals (Mo and W), for 8 reactions containing Fe, Cu, Nb and Re complexes. Finally, for the whole set of 111 reactions, the DLPNO-CCSD(T), B3LYP-D3 and PBE0-D3 methods turned out to be the best performers, both providing MUE below 5.0 kcal/mol. Since DFT results cannot be systematically improved and large non-systematic deviations of 20-30 kcal/mol were obtained even for best performers, our results indicates that current DFT methods are still unable to provide robust predictions in transition metal thermochemistry, at least for the functionals explored in this work. The same conclusion holds for both DLPNO-CCSD(T) and canonical CCSD(T) methods when used entirely as out-of-the-box. However if careful investigation core correlation is performed, relativistic effects are properly included and the quality of the reference wave function is properly checked, CCSD(T) methods can still provide good quality results that might be even used to validate DFT methods, due to paucity of accurate thermodynamic data for realistic-size transition metal complexes.We gratefully acknowledge Dr. Valery V. Sliznev, Ivanovo State University of Chemistry and
Technology, The Russian Federation and Prof. Dr. Takeshi Noro, Hokkaido University, Japan
for helpful discussions and correspondence. We also gratefully acknowledge Prof. Dr. José A.
Martinho Simões, University of Lisbon, Portugal for providing us the original references on
formation enthalpies of some organometallic species published on NIST webbook. The research
reported in this publication was supported by funding from King Abdullah University of Science
and Technology (KAUST). For computer time, this research used the resources of the
Supercomputing Laboratory at King Abdullah University of Science and Technology (KAUST)
in Thuwal, Saudi Arabia
Occurrence and stability of lone pair-π stacking interactions between ribose and nucleobases in functional RNAs
No full textThe specific folding pattern and function of RNA molecules lies in various weak interactions, in addition to the strong base-base pairing and stacking. One of these relatively weak interactions, characterized by the stacking of the O4' atom of a ribose on top of the heterocycle ring of a nucleobase, has been known to occur but has largely been ignored in the description of RNA structures. We identified 2015 ribose-base stacking interactions in a high-resolution set of non-redundant RNA crystal structures. They are widespread in structured RNA molecules and are located in structural motifs other than regular stems. Over 50% of them involve an adenine, as we found ribose-adenine contacts to be recurring elements in A-minor motifs. Fewer than 50% of the interactions involve a ribose and a base of neighboring residues, while approximately 30% of them involve a ribose and a nucleobase at least four residues apart. Some of them establish inter-domain or inter-molecular contacts and often implicate functionally relevant nucleotides. In vacuo ribose-nucleobase stacking interaction energies were calculated by quantum mechanics methods. Finally, we found that lone pair-π stacking interactions also occur between ribose and aromatic amino acids in RNA-protein complexes
Orbitales localisées pour les interactions intermoléculaires
No full textWe study in this thesis intermolecular interactions through a localized orbitals point of view. This concerns on one hand the intermolecular interactions generated by the occupied localized orbitals such as the electrostatic interaction, and on the other hand the intermolecular interactions like the dispersion interaction that involve virtual orbitals. We evaluate in a first part the electrostatic interactions on frozen monomer charge densities provided by multipolar distributions on occupied localized orbitals. These give chemically meaningful representations of molecular charge densities. We show that multipolar distributions on localized orbitals are suitable to describe intermolecular electrostatic interactions if the interaction is truncated to a suitable order, making localized orbitals potentially interesting to model electrostatic interactions in a force field. We use then the properties of a priori constructed localized orbitals on a complex in order to define a reference multipolar interaction for the electrostatic interaction of relaxed charge densities. We evaluate hence the capacity of multipolar distributions based on relaxed localized orbitals to decribe the relaxed electrostatic interaction. In a second part, localizing both occupied and virtual orbitals in an intermolecular framework allows us to attribute the orbitals of a noncovalent system to each of its fragments (and to divide the excitations by classes), and select in a further step only the most relevant excitations to the intermolecular post-Hartree-Fock correlation energy. We propose two different methods we developped in this work to select the excitations in the general framework of the range separated density functional theory (DFT) coupled to the random phase approximation (RPA). The first method is based on a simple energetic criterion while the other is based on a selection of only one class, namely the dispersion-type excitations. We show afterwards both the usefulness and the limits of those two methods of selection on complexes with various types of interaction.Nous réalisons dans cette thèse l'étude d'interactions intermoléculaires d'un point de vue d'orbitales localisées. Cela concerne d'une part les interactions intermoléculaires produites par des orbitales localisées occupées comme l'interaction électrostatique, et d'autre part les interactions intermoléculaires qui engagent aussi les orbitales localisées virtuelles comme l'interaction de dispersion. Nous évaluons dans un premier temps les interactions électrostatiques produites par des distributions multipolaires en orbitales localisées, qui donnent une représentation chimique intuitive d'une densité de charges moléculaire. Nous montrons que les distributions multipolaires en orbitales localisées sont raisonnables pour décrire les interactions électrostatiques des densités de charges gelées si l'interaction multipolaire est tronquée à un ordre bien choisi, ce qui rend les orbitales localisées potentiellement intéressantes pour modéliser les interactions électrostatiques dans un champ de force. Nous utilisons ensuite les propriétés des orbitales localisées a priori dans un complexe pour définir une référence multipolaire dans le cas de l'interaction électrostatique des densités de charges relaxées. Nous évaluons ensuite la capacité de distributions multipolaires issues d'orbitales localisées relaxées pour décrire l'interaction électrostatique relaxée. Dans un second temps, localiser les orbitales occupées et virtuelles dans un cadre intermoléculaire nous permet d'une part d'attribuer des orbitales à chaque fragment d'un système fragmenté non covalent, et donc de diviser les excitations en classes et sélectionner uniquement les excitations les plus importantes à l'énergie de corrélation intermoléculaire post-Hartree-Fock. Nous proposons deux méthodes différentes que nous avons développé dans cette thèse pour sélectionner des excitations dans le cadre général de la DFT à séparation de portée couplée à l'approximation des phases aléatoires (RPA). La première méthode de sélection est basée sur un simple critère énergetique tandis que la seconde est basée sur la sélection d'une seule classe d'excitation à savoir la classe de dispersion. Enfin, nous montrons l'intérêt et les limites de ces deux méthodes de sélection pour des complexes à interactions variées
Solid-State NMR and DFT Studies on the Formation of Well-Defined Silica-Supported Tantallaaziridines: From Synthesis to Catalytic Application
No full textSingle-site, well-defined, silica-supported tantallaaziridine intermediates [Si-O-Ta((2)-NRCH2)(NMe2)(2)] [R=Me (2), Ph (3)] were prepared from silica-supported tetrakis(dimethylamido)tantalum [Si-O-Ta(NMe2)(4)] (1) and fully characterized by FTIR spectroscopy, elemental analysis, and H-1,C-13 HETCOR and DQ TQ solid-state (SS) NMR spectroscopy. The formation mechanism, by -H abstraction, was investigated by SS NMR spectroscopy and supported by DFT calculations. The C-H activation of the dimethylamide ligand is favored for R=Ph. The results from catalytic testing in the hydroaminoalkylation of alkenes were consistent with the N-alkyl aryl amine substrates being more efficient than N-dialkyl amines
Theoretical Characterization of the H-Bonding and Stacking Potential of Two Nonstandard Nucleobases Expanding the Genetic Alphabet
No full textWe report a quantum chemical characterization of the non-natural (synthetic) H-bonded base pair formed by 6-amino-5-nitro-2(1H)-pyridone (Z) and 2-aminoimidazo[1,2-a]-1,3,5-triazin-4(8H)-one (P). The Z:P base pair, orthogonal to the classical G:C base pair, has been introduced into DNA molecules to expand the genetic code. Our results indicate that the Z:P base pair closely mimics the G:C base pair in terms of both structure and stability. To clarify the role of the NO2 group on the C5 position of the Z base, we compared the stability of the Z:P base pair with that of base pairs having different functional groups at the C5 position of Z. Our results indicate that the electron-donating/-withdrawing properties of the group on C5 have a clear impact on the stability of the Z:P base pair, with the strong electron-withdrawing nitro group achieving the largest stabilizing effect on the H-bonding interaction and the strong electron-donating NH2 group destabilizing the Z:P pair by almost 4 kcal/mol. Finally, our gas-phase and in-water calculations confirm that the Z-nitro group reinforces the stacking interaction with its adjacent purine or pyrimidine ring
