Guiding Competitive Binding Assays Using Protein-Protein Interaction Prediction: The HER2-Affitin Use Case.

Affitins are a class of small artificial proteins, designed as alternatives to antibodies for therapeutic, diagnostic, and biotechnological applications. Recent patents by Bracco Imaging S.p.

Behind the glow: unveiling the nature of NanoLuc reactants and products.

Due to the largely recognized utility of bioluminescence in many fields, a wide variety of luciferase-luciferin systems have been investigated in order to find the best-suited for a number of different applications. The collected knowledge has allowed the identification of a few necessary, or at least desirable, properties, such as bright luminescence, low background signal and small dimension of the enzyme that must exhibit structural stability at operating conditions. The NanoLuc-furimazine pair seems to meet all these requirements, but the mechanism of the reaction and the characteristics of the species responsible for the emission remain unknown.

CO Oxidation Mechanism of Silver-Substituted Mo/Cu CO-Dehydrogenase - Analogies and Differences to the Native Enzyme.

The aerobic oxidation of carbon monoxide to carbon dioxide is catalysed by the Mo/Cu-containing CO-dehydrogenase enzyme in the soil bacterium Oligotropha carboxidovorans, enabling the organism to grow on the small gas molecule as carbon and energy source. It was shown experimentally that silver can be substituted for copper in the active site of Mo/Cu CODH to yield a functional enzyme. In this study, we employed QM/MM calculations to investigate whether the reaction mechanism of the silver-substituted enzyme is similar to that of the native enzyme.

Large barrier behavior of the rate constant from the diffusion equation.

Many processes in chemistry, physics, and biology depend on thermally activated events in which the system changes its state by surmounting an activation barrier. Examples range from chemical reactions to protein folding and nucleation events. Parameterized forms of the mean field potential are often employed in the stochastic modeling of activated processes.

Evaluation of docking procedures reliability in affitins-partners interactions.

Affitins constitute a class of small proteins belonging to Sul7d family, which, in microorganisms such as , bind DNA preventing its denaturation. Thanks to their stability and small size (60-66 residues in length) they have been considered as ideal candidates for engineering and have been used for more than 10 years now, for different applications. The individuation of a mutant able to recognize a specific target does not imply the knowledge of the binding geometry between the two proteins.

How general is the effect of the bulkiness of organic ligands on the basicity of metal-organic catalysts? H-evolving Mo oxides/sulphides as case studies.

Tailoring the activity of an organometallic catalyst usually requires a targeted ligand design. Tuning the ligand bulkiness and tuning the electronic properties are popular approaches, which are somehow interdependent because substituents of different sizes within ligands can determine the occurrence of different degrees of inductive effects. Ligand basicity, in particular, turned out to be a key property for the modulation of protonation reactions occurring at the metals in complexes bearing organophosphorus ligands; however, when the same reactions take place in a polar organic solvent, their energetics becomes dependent on the trade-off between ligand basicity and bulkiness, with the polarity of the solvent playing a key role in this regard [Bancroft , , 1986, , 3675; Rovaletti , , 2018, , e3748].

Partition of the Reactive Species of the Suzuki-Miyaura Reaction between Aqueous and Micellar Environments.

The Suzuki-Miyaura reaction between the aryl halide () and the phenyl boronic acid (), in the presence of the palladium(0) complex () as catalyst, gives the cross-coupling product () in quantitative yield when performed in basic aqueous solution of the nonionic surfactant Kolliphor-EL (K-EL). The partition between the aqueous and micellar environments of the species of this reaction has been investigated by means of Molecular Dynamics (MD) simulations. Starting from the K-EL molecules dispersed in water, a micelle model has been generated by MD simulations, adopting the 2016H66 force field.

Can Water Act as a Nucleophile in CO Oxidation Catalysed by Mo/Cu CO-Dehydrogenase? Answers from Theory.

The aerobic CO dehydrogenase from Oligotropha carboxidovorans is an environmentally crucial bacterial enzyme for maintenance of subtoxic concentration of CO in the lower atmosphere, as it allows for the oxidation of CO to CO which takes place at its Mo-Cu heterobimetallic active site. Despite extensive experimental and theoretical efforts, significant uncertainties still concern the reaction mechanism for the CO oxidation. In this work, we used the hybrid quantum mechanical/molecular mechanical approach to evaluate whether a water molecule present in the active site might act as a nucleophile upon formation of the new C-O bond, a hypothesis recently suggested in the literature.

Dynamical Behavior and Conformational Selection Mechanism of the Intrinsically Disordered Sic1 Kinase-Inhibitor Domain.

Intrinsically Disordered Peptides and Proteins (IDPs) in solution can span a broad range of conformations that often are hard to characterize by both experimental and computational methods. However, obtaining a significant representation of the conformational space is important to understand mechanisms underlying protein functions such as partner recognition. In this work, we investigated the behavior of the Sic1 Kinase-Inhibitor Domain (KID) in solution by Molecular Dynamics (MD) simulations.

Role of the carbon defects in the catalytic oxygen reduction by graphite nanoparticles: a spectromagnetic, electrochemical and computational integrated approach.

The chemical groups present at the surface of graphite have been thought for a long time to be mainly responsible for its catalytic activity in the oxygen reduction reaction. Recently, it was proposed that the surface defects of graphite also significantly contribute to promote this reaction. Although the behaviour of surface defects has been reported, only few comments have been dedicated to their involvement in the mechanism and the possible intermediate species in the oxygen reduction reaction.

The Challenging Description of Carbon Monoxide Oxidation as Catalyzed by Molybdenum-Copper CO Dehydrogenase.

Carbon monoxide (CO) is a highly toxic gas to many living organisms. However, some microorganisms are able to use this molecule as the sole source of carbon and energy. Soil bacteria such as the aerobic are responsible for the annual removal of about 210 tons of CO from the atmosphere.

Quantum Stochastic Trajectories: The Fokker-Planck-Bohm Equation Driven by the Reduced Density Matrix.

The quantum molecular trajectory is the deterministic trajectory, arising from the Bohm theory, that describes the instantaneous positions of the nuclei of molecules by assuring the agreement with the predictions of quantum mechanics. Therefore, it provides the suitable framework for representing the geometry and the motions of molecules without neglecting their quantum nature. However, the quantum molecular trajectory is extremely demanding from the computational point of view, and this strongly limits its applications.

Quantum stochastic trajectories: the Smoluchowski-Bohm equation.

Molecular systems are quantum systems, but the complete characterization of molecular motions within a fully quantum framework might appear to be an unfeasible task because it would require that the actual nuclear positions are established at any time. One would like to use a quantum molecular trajectory that defines the instantaneous nuclear positions and satisfies the predictions of quantum mechanics in terms of its statistical properties. Even though it can be proven that the single Bohm trajectory provides a representation of the quantum molecular trajectory, this solves the issue only on a theoretical ground: exact solutions of the Schrödinger-Bohm dynamical system are extremely computationally demanding.

Thermal Pure States for Finite and Isolated Quantum Systems.

We study an ensemble of quantum pure states, the thermalization resilient ensemble (TRE), providing the statistical characterization of the thermal equilibrium of isolated quantum systems. Following a previous work where the ensemble was defined based on the invariance of the average populations upon thermal contact of identical systems, here we introduce a general methodology to generate quantum states according to the TRE statistic. The sampling is employed to characterize the ensemble distribution of thermodynamic functions like the entropy, internal energy, and temperature.

Quantum Molecular Trajectory and Its Statistical Properties.

Despite the quantum nature of molecules, classical mechanics is often employed to describe molecular motions that play a fundamental role in a wide range of phenomena including chemical reactions. This is due to the need of assigning well-defined positions to the atomic nuclei during the time evolution of the system in order to describe unambiguously the molecular motions, whereas quantum mechanics provides information on probabilistic nature only. One would like to employ a quantum molecular trajectory that defines rigorously the instantaneous nuclear positions and, simultaneously, guarantees the conservation of all quantum mechanics predictions unlike the classical trajectory.

A theoretical study on the reactivity of the Mo/Cu-containing carbon monoxide dehydrogenase with dihydrogen.

The Mo/Cu-dependent CO dehydrogenase from Oligotropha carboxidovorans is an enzyme that is able to catalyze CO oxidation to CO2; moreover, it can also oxidize H2, thus eliciting a characteristic EPR signal. Interestingly, the Ag-substituted enzyme form proved unable to catalyze H2 oxidation. In the present contribution, we characterized the reactivity of the enzyme with H2 by quantum-chemical calculations.

Quantum Statistical Ensemble Resilient to Thermalization.

The sampling of the wave function within a suitable ensemble is an important tool in the statistical analysis of a molecule interacting with its environment. The uniform statistical distribution of quantum pure states in an active space is often the privileged choice. However, such a distribution with constant average populations of eigenstates is not preserved upon the interaction between quantum systems.

Influence of key amino acid mutation on the active site structure and on folding in acetyl-CoA synthase: a theoretical perspective.

Ad hoc quantum chemical modeling of the acetyl-CoA synthase local structure and folding allowed us to identify an unprecedented coordination mode of histidine sidechain to protein-embedded metal ions.

Quantum mechanical methods for the investigation of metalloproteins and related bioinorganic compounds.

It is well known that transition metal ions are often bound to proteins, conveying very specific functional properties. In fact, metalloproteins play crucial biological roles in the transport and activation of small molecules such as H2, O2, and N2, as well as in several other biochemical processes. However, even if the presence of transition metals in the active site of proteins allows a very rich biochemistry, the experimental disclosure of structure-activity relationships in metalloproteins is generally difficult exactly because of the presence of transition metals, which are intrinsically characterized by a very versatile and often elusive chemistry.

Computational Investigation on the Spectroscopic Properties of Thiophene Based Europium β-Diketonate Complexes.

The adiabatic transition energies from the lowest triplet states of four Europium tris β-diketonate/phenantroline complexes have been determined in vacuo and in dicholomethane solution by the ΔSCF approach at the density functional theory level, using the PBE1PBE and the CAM-B3LYP hybrid functionals. The calculated adiabatic transition energies have been compared with the experimental 0-0 transitions of each complex determined from phosphorescence spectra of the corresponding Gd(3+) complexes and followed by direct comparison between simulated and experimental spectra line shapes. For compound 1, the Eu(TTA)3Phen system, triplet states other than the lowest one and conformational isomers other than the one present in the crystallographic structure have been considered.

Does the environment around the H-cluster allow coordination of the pendant amine to the catalytic iron center in [FeFe] hydrogenases? Answers from theory.

[FeFe] hydrogenases are H2-evolving enzymes that feature a diiron cluster in their active site (the [2Fe]H cluster). One of the iron atoms has a vacant coordination site that directly interacts with H2, thus favoring its splitting in cooperation with the secondary amine group of a neighboring, flexible azadithiolate ligand. The vacant site is also the primary target of the inhibitor O2.

Synthesis and characterization of a paramagnetic sialic acid conjugate as probe for magnetic resonance applications.

Magnetic Resonance Imaging (MRI) using paramagnetic systems as contrast agents is receiving increased attention as diagnostic tool in the clinic. At the same time, NMR of paramagnetic systems can also be applied in biochemical fields; for example, the use of Paramagnetic Relaxation Enhancement (PRE) allows structure refinement and the analysis of transient dynamic processes involved in macromolecular complex formation. Herein we report the synthesis and computational characterization of a new DOTA-like sialic acid conjugate, which can be used both in MRI and PRE applications when coordinated to a suitable paramagnetic metal.

NIR emitting ytterbium chelates for colourless luminescent solar concentrators.

A new oxyiminopyrazole-based ytterbium chelate enables NIR emission upon UV excitation in colorless single layer luminescent solar concentrators for building integrated photovoltaics.

Beyond quantum microcanonical statistics.

Descriptions of molecular systems usually refer to two distinct theoretical frameworks. On the one hand the quantum pure state, i.e.

Emergence of equilibrium thermodynamic properties in quantum pure states. II. Analysis of a spin model system.

A system composed of identical spins and described by a quantum mechanical pure state is analyzed within the statistical framework presented in Part I of this work. We explicitly derive the typical values of the entropy, of the energy, and of the equilibrium reduced density matrix of a subsystem for the two different statistics introduced in Part I. In order to analyze their consistency with thermodynamics, these quantities of interest are evaluated in the limit of large number of components of the isolated system.