The research on carbon dots is evolving and expanding very rapidly. A high-tech overview for academia and industry is needed to modernize carbon dots in biological applications. This book covers the ...use of carbon dots in biology, medicine, and pharmacy: synthesis, properties and applications, obstacles in exploiting these materials, and future research prospects. The reader is able to explore the wide scope of carbon dots in the global market.
The Candida genus is composed of opportunistic pathogens that threaten public health. Given the increase in resistance to current drugs, it is necessary to develop new drugs to treat infections by ...these pathogens. Antimicrobial peptides are promising alternative molecules with low cost, broad action spectrum and low resistance induction. This study aimed to clarify the action mechanisms of synthetic peptides against Candida albicans.
The mode of action of the anticandidal peptides Mo-CBP3-PepIII were analyzed through molecular dynamics and quantum biochemistry methods against Exo-β-1,3-glucanase (EXG), vital to cell wall metabolism. Furthermore, scanning electron (SEM) and fluorescence (FM) microscopies were employed to corroborate the in silico data.
Mo-CBP3-PepIII strongly interacted with EXG (−122.2 kcal mol−1) at the active site, higher than the commercial inhibitor pepstatin. Also, molecular dynamics revealed the insertion of Mo-CBP3-PepIII into the yeast membrane. SEM analyses revealed that Mo-CBP3-PepIII induced cracks and scars of the cell wall and FM analyses confirmed the pore formation on the Candida membrane.
Mo-CBP3-PepIII has strong potential as a new drug with a broad spectrum of action, given its different mode of action compared to conventional drugs.
•Mo-CBP3-PepIII interacts with Exo-β-1,3-glucanase stronger than conventional inhibitor.•Dynamics simulation revealed how Mo-CBP3-PepIII penetrates in the yeast membrane.•SEM analysis revealed cell wall damage in C. albicans induced by Mo-CBP3-PepIII.•Fluorescence microscopy analysis revealed pore formation in the C. albicans membrane.•Mo-CBP3-PepIII induces ROS overproduction C. albicans cells.
The Zika virus protease NS2B-NS3 has a binding site formed with the participation of a H51-D75-S135 triad presenting two forms, active and inactive. Studies suggest that the inactive conformation is ...a good target for the design of inhibitors. In this paper, we evaluated the co-crystallized structures of the protease with the inhibitors benzoic acid (5YOD) and benzimidazole-1-ylmethanol (5H4I). We applied a protocol consisting of two steps: first, classical molecular mechanics energy minimization followed by classical molecular dynamics were performed, obtaining stabilized molecular geometries; second, the optimized/relaxed geometries were used in quantum biochemistry and molecular mechanics/Poisson–Boltzmann surface area (MM-PBSA) calculations to estimate the ligand interactions with each amino acid residue of the binding pocket. We show that the quantum-level results identified essential residues for the stabilization of the 5YOD and 5H4I complexes after classical energy minimization, matching previously published experimental data. The same success, however, was not observed for the MM-PBSA simulations. The application of quantum biochemistry methods seems to be more promising for the design of novel inhibitors acting on NS2B-NS3.
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•Quantum biochemistry calculation of the binding energy of SERMS with OHT and RAL.•SERMs-OHT binds more strongly when compared to SERMs-RAL.•Selective estrogen receptor modulators are ...very effective against breast cancer.•MFCC scheme was used for individual contribution of each amino acid residue.
In this work we employed quantum biochemistry methods based on the density functional theory (DFT) model and the MFCC (Molecular Fractionation with Conjugate Caps) scheme to unveil the detailed binding energy features of the tissue-selective synthetic agents SERMs (selective estrogen receptor modulators) 4-hydroxytamoxifen (OHT) and raloxifene (RAL), widely used in the breast cancer treatment, co-crystallized with the estrogen receptor α (ERα). Our theoretical/computational results demonstrated that the total binding energies of OHT and RAL to the ERα ligand-pocket correlate with the experimental binding affinity. Besides, we found that SERMs-OHT binds stronger when compared to SERMs-RAL, confirming experimental data, whose main contributions to the total SERMs-ERα binding energy are due to the amino acid residues in decreasing sequence D351>E542>D538>E353>E423, an important information to understand their binding mechanisms.
Quantum chemical (QC) calculations provide a basis for deriving a microscopic understanding of enzymes and photobiological systems. Here we describe how QC models can be used to explore the ...electronic structure, dynamics, and energetics of biomolecules. We introduce the hybrid quantum mechanics/classical mechanics (QM/MM) approach, where a quantum mechanically described system of interest is embedded in a classically described force field representation of the biochemical surroundings. We also discuss the QM cluster model approach, as well as embedding theories, that provide complementary methodologies to model quantum mechanical effects in biomolecules. The chapter also provides some practical guides for building quantum biochemical models using the quinone reduction catalysis in respiratory complex I and a model reaction in solution as examples.
Quantum aspects of life Abbott, Derek; Devies, Paul C. W; Pati, Arun K
2008., 2008, 2008-09-12
eBook
This book presents the hotly debated question of whether quantum mechanics plays a non-trivial role in biology. In a timely way, it sets out a distinct quantum biology agenda. The burgeoning fields ...of nanotechnology, biotechnology, quantum technology, and quantum information processing are now strongly converging. The acronym BINS, for Bio-Info-Nano-Systems, has been coined to describe the synergetic interface of these several disciplines.
As the dopamine D3R receptor is a promising target for schizophrenia treatment, an improved understanding of the binding of existing antipsychotics to this receptor is crucial for the development of ...new potent and more selective therapeutic agents. In this work, we have used X-ray cocrystallization data of the antagonist eticlopride bound to D3R as a template to predict, through docking essays, the placement of the typical antipsychotic drug haloperidol at the D3R receptor binding site. Afterward, classical and quantum mechanics/molecular mechanics (QM/MM) computations were employed to improve the quality of the docking calculations, with the QM part of the simulations being accomplished by using the density functional theory (DFT) formalism. After docking, the calculated QM improved total interaction energy E QMDI = −170.1 kcal/mol was larger (in absolute value) than that obtained with classical molecular mechanics improved (E CLDI = −156.3 kcal/mol) and crude docking (E CRDI = −137.6 kcal/mol) procedures. The QM/MM computations reveal the pivotal role of the Asp110 amino acid residue in the D3R haloperidol binding, followed by Tyr365, Phe345, Ile183, Phe346, Tyr373, and Cys114. Besides, it highlights the relevance of the haloperidol hydroxyl group axial orientation, which interacts with the Tyr365 and Thr369 residues, enhancing its binding to dopamine receptors. Finally, our computations indicate that functional substitutions in the 4-clorophenyl and in the 4-hydroxypiperidin-1-yl fragments (such as C3H and C12H hydrogen replacement by OH or COOH) can lead to haloperidol derivatives with distinct dopamine antagonism profiles. The results of our work are a first step using in silico quantum biochemical design as means to impact the discovery of new medicines to treat schizophrenia.
Risperidone is an atypical antipsychotic used in the treatment of schizophrenia and of symptoms of irritability associated with autism spectrum disorder (ASD). Its main action mechanism is the ...blockade of D2-like receptors acting over positive and negative symptoms of schizophrenia with small risk of extrapyramidal symptoms (EPS) at doses corresponding to low/moderate D2 occupancy. Such a decrease in the side effect incidence can be associated with its fast unbinding from D2 receptors in the nigrostriatal region allowing the recovery of dopamine signaling pathways. We performed docking essays using risperidone and the D3 receptor crystallographic data and results suggested two possible distinct orientations for risperidone at the binding pocket. Orientation 1 is more close to the opening of the binding site and has the 6-fluoro-1,2 benzoxazole fragment toward the bottom of the D3 receptor cleft, while orientation 2 is deeper inside the binding pocket with the same fragment toward to the receptor surface. In order to unveil the implications of these two binding orientations, classical molecular dynamics and quantum biochemistry computations within the density functional theory formalism and the molecular fractionation with conjugate caps framework were performed. Quantum mechanics/molecular mechanics suggests that orientation 2 (considering the contribution of Glu90) is slightly more energetically stable than orientation 1 with the main contribution coming from residue Asp110. The residue Glu90, positioned at the opening of the binding site, is closer to orientation 1 than 2, suggesting that it may have a key role in stability through attractive interaction with risperidone. Therefore, although orientations 1 and 2 are both likely to occur, we suggest that the occurrence of the first may contribute to the reduction of side effects in patients taking risperidone due to the reduction of dopamine receptor occupancy in the nigrostriatal region through a mechanism of fast dissociation. The atypical effect may be obtained simply by either delaying D3R full blockage by spatial hindrance of orientation 1 at the binding site or through an effective blockade followed by orientation 1 fast dissociation. While the molecular interpretation suggested in this work shed some light on the potential molecular mechanisms accounting for the reduced extrapyramidal symptoms observed during risperidone treatment, further studies are necessary in order to evaluate the implications of both orientations during the receptor activation/inhibition. Altogether these data highlight important hot spots in the dopamine receptor binding site bringing relevant information for the development of novel/derivative agents with atypical profile.
Density Functional Theory is situated within the evolution of Quantum Chemistry as a facilitator of computations and a provider of new, chemical insights. The importance of the latter branch of DFT, ...conceptual DFT is highlighted following Parr's dictum "to calculate a molecule is not to understand it". An overview is given of the most important reactivity descriptors and the principles they are couched in. Examples are given on the evolution of the structure-property-wave function triangle which can be considered as the central paradigm of molecular quantum chemistry to (for many purposes) a structure-property-density triangle. Both kinetic as well as thermodynamic aspects can be included when further linking reactivity to the property vertex. In the field of organic chemistry, the ab initio calculation of functional group properties and their use in studies on acidity and basicity is discussed together with the use of DFT descriptors to study the kinetics of SN2 reactions and the regioselectivity in Diels Alder reactions. Similarity in reactivity is illustrated via a study on peptide isosteres. In the field of inorganic chemistry non empirical studies of adsorption of small molecules in zeolite cages are discussed providing Henry constants and separation constants, the latter in remarkable good agreement with experiments. Possible refinements in a conceptual DFT context are presented. Finally an example from biochemistry is discussed : the influence of point mutations on the catalytic activity of subtilisin.
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