The antioxidant properties of 21 proteinogenic amino acids (AAs) and 3,4-dioxophenylanine (DOPA) have been studied in implicit water using density functional theory (DFT). All the calculations have ...been performed according to three oxidation mechanisms: (1) hydrogen-atom transfer (HAT); (2) single electron transfer followed by proton transfer (SET-PT); and (3) sequential proton-loss electron transfer (SPLET). As a result, five AAs with the highest antioxidant capacity have been established: DOPA, selenocysteine (Sec), tyrosine (Tyr), cysteine (Cys), and tryptophan (Trp). Also, global reactivity in terms of hardness/softness has been evaluated, as well as Fukui indices of local reactivity. Trp has been determined as the most reactive molecule, whereas selenium atom of Sec has been established as the most reactive atom. All the findings are in agreement with the recent literature on both experimental and theoretical studies of amino acids antioxidant activity. However, to the best of my knowledge, the calculations for one electron redox reactions of zwitterionic amino acids in implicit water have been performed for the first time.The antioxidant properties of 21 proteinogenic amino acids (AAs) and 3,4-dioxophenylanine (DOPA) have been studied in implicit water using density functional theory (DFT). All the calculations have been performed according to three oxidation mechanisms: (1) hydrogen-atom transfer (HAT); (2) single electron transfer followed by proton transfer (SET-PT); and (3) sequential proton-loss electron transfer (SPLET). As a result, five AAs with the highest antioxidant capacity have been established: DOPA, selenocysteine (Sec), tyrosine (Tyr), cysteine (Cys), and tryptophan (Trp). Also, global reactivity in terms of hardness/softness has been evaluated, as well as Fukui indices of local reactivity. Trp has been determined as the most reactive molecule, whereas selenium atom of Sec has been established as the most reactive atom. All the findings are in agreement with the recent literature on both experimental and theoretical studies of amino acids antioxidant activity. However, to the best of my knowledge, the calculations for one electron redox reactions of zwitterionic amino acids in implicit water have been performed for the first time.
Aptamers are nucleic acid analogues of antibodies with high affinity to different targets, such as cells, viruses, proteins, inorganic materials, and coenzymes. Empirical approaches allow the design ...of in vitro aptamers that bind particularly to a target molecule with high affinity and selectivity. Theoretical methods allow significant expansion of the possibilities of aptamer design. In this study, we review theoretical and joint theoretical-experimental studies dedicated to aptamer design and modeling. We consider aptamers with different targets, such as proteins, antibiotics, organophosphates, nucleobases, amino acids, and drugs. During nucleic acid modeling and in silico design, a full set of in silico methods can be applied, such as docking, molecular dynamics (MD), and statistical analysis. The typical modeling workflow starts with structure prediction. Then, docking of target and aptamer is performed. Next, MD simulations are performed, which allows for an evaluation of the stability of aptamer/ligand complexes and determination of the binding energies with higher accuracy. Then, aptamer/ligand interactions are analyzed, and mutations of studied aptamers made. Subsequently, the whole procedure of molecular modeling can be reiterated. Thus, the interactions between aptamers and their ligands are complex and difficult to understand using only experimental approaches. Docking and MD are irreplaceable when aptamers are studied in silico.
Tyrosine (Tyr) is involved in the synthesis of neurotransmitters, catecholamines, thyroid hormones, etc. Multiple pathologies are associated with impaired Tyr metabolism. Silver nanoclusters (Ag NCs) ...can be applied for colorimetric, fluorescent, and surface-enhanced Raman spectroscopy (SERS) detection of Tyr. However, one should understand the theoretical basics of interactions between Tyr and Ag NCs. Thereby, we calculated the binding energy (E
) between Tyr and Ag
(n = 1-8; q = 0-2) NCs using the density functional theory (DFT) to find the most stable complexes. Since Ag NCs are synthesized on Tyr in an aqueous solution at pH 12.5, we studied Tyr
, semiquinone (SemiQ
), and Tyr
. Ag
and Ag
had the highest E
. The absorption spectrum of Tyr
significantly red-shifts with the attachment of Ag
, which is prospective for colorimetric Tyr detection. Ag
interacts with all functional groups of SemiQ
(phenolate, amino group, and carboxylate), which makes detection of Tyr possible due to band emergence at 1324 cm
in the vibrational spectrum. The ground state charge transfer between Ag and carboxylate determines the band emergence at 1661 cm
in the Raman spectrum of the SemiQ
-Ag
complex. Thus, the prospects of Tyr detection using silver nanoclusters were demonstrated.
Metal nanoclusters (NCs) have gained much attention in the last decade. In solution, metal nanoclusters can be stabilized by proteins, and, thus, exhibit many advantages in biocatalysis, biosensing, ...and bioimaging. In spite of much progress in the synthesis of polypeptide-stabilized gold (Au) clusters, their structure, as well as amino acid-cluster and amino acid-Au
+
interactions, remain poorly understood. It is not entirely clear which amino acid (AA) residues and sites in the protein are preferred for binding. The understanding of NC-protein interactions and how they evolve in the polypeptide templates is the key to designing Au NCs. In this work, binding of gold ion Au
+
and diatomic neutral gold nanocluster Au
2
with a full set of α-proteinogenic amino acids is studied using Density Functional Theory (DFT) and the
ab initio
RI-MP2 method in order to find the preferred sites of gold interaction in proteins. We demonstrated that the interaction of gold cations and clusters with protonated and deprotonated amino acid residues do not differ greatly. The binding affinity of AAs to the Au
2
cluster increases in the following order: Cys(−H
+
) > Asp(−H
+
) > Tyr(−H
+
) > Glu(−H
+
) > Arg > Gln, His, Met > Asn, Pro, Trp > Lys, Tyr, Phe > His(+H
+
) > Asp > Lys(+H
+
) > Glu, Leu > Arg(+H
+
) > Ile, Val, Ala > Thr, Ser > Gly, Cys, which agrees with the available experimental data that gold cluster synthesis occurs in a wide range of pH - amino acid residues with different protonation states are involved in this process. The significant difference in the binding energy of metal atoms with nucleobases and amino acids apparently means that unlike on DNA templates, neutral metal atoms are strongly bound to amino acid residues and can't freely diffuse in a polypeptide globula. This fact allows one to conclude that formation of metal NCs in proteins occurs through the nucleation of reduced Au atoms bound to the neighboring amino acid residues, and the flexibility of the amino acid residue side-chains and protein chain as a whole plays a significant role in this process.
Our calculations showed that amino acids stabilize gold nanoclusters; binding energy between organics and gold is higher than between organics and silver.
Binding of silver ion (Ag
+
) and two atomic neutral silver cluster (Ag
2
) with a set of amino acids has been studied using Density Functional Theory (DFT) and ab initio MP2 method. We show that ...binding energy with Ag
2
is higher for deprotonated anionic amino acids. Cysteine, aspartic acid, and tyrosine with deprotonated side chain exhibit the highest binding energy (
G
bind
) values among all the amino acids: − 30.1 kcal mol
−1
, − 30.7 kcal mol
−1
, and − 30.9 kcal mol
−1
, respectively. Binding energies of deprotonated cysteine, glutamic acid, tyrosine, and aspartic acid with silver ion Ag
+
are reported here for the first time. Natural bond orbital (NBO) analysis has also been performed to calculate charge transfer, natural populations, occupancies, and Wiberg bond indices of the amino acid–Ag
2
complexes. Atoms-in-molecules (AIM) theory was used to establish the nature of interactions. It was shown that, in most cases, the bonds between amino acid and Ag
2
cluster are partially electrostatic and partially covalent.
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•Interactions of phenylalanine (Phe) and Au clusters (NCs) have been studied using theory for the first time.•The NCs with magic number of electrons were the most favorable ...ones.•Metal-ligand intracomplex interactions were partially covalent and partially electrostatic.•The presence of gold significantly enhanced the Raman spectra signal of Phe.
Nanomaterials are widely used nowadays in industry and medicine. The specific properties of gold nanoclusters (Au NCs) are chemical stability, low cytotoxicity, low photobleaching, high sensitivity to the molecular environment. This set of properties allows to use Au NCs as nanosensors in bioimaging and diagnostics. We have investigated gold cluster complexes with proteinogenic amino acid phenylalanine (Phe). Detection of phenylalanine is essential for diagnostics of phenylketonuria, vitiligo, sclerosis, cancer, tuberculosis, etc. We have studied the complexes of Phe with Aunq clusters with atomic number equal 1–6, 8, 20 and a charge equal 0–2. We have established that the clusters Au40, Au21+ and Au32+ form the most stable complexes with Phe among NCs with charge 0, +1 and + 2, respectively. Intracomplex interactions have been studied using Atoms-In-Molecules (AIM) theory and Natural Bond Orbital (NBO) analysis. It has been shown that metal–ligand intracomplex interactions are partially covalent and partially electrostatic. Also, we have simulated the UV–vis absorption and Raman spectra of the Phe-Au NCs. We have established that the clusters possess prospective features if being used for colorimetric and Raman detection of Phe. Au20 cluster is remarkable for its six-times enhancement of the Raman signal. Moreover, our study provides insights into metal–ligand interactions for clusters synthesized inside a polypeptide globula. Hence, to the best of our knowledge this is a first attempt to perform a detailed analysis of Phe interactions with gold using quantum chemical calculations.
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•Interactions between pterin (Ptr) and Ag clusters have been explored using quantum chemistry.•It has been established that Ptr-Ag32+ complex is the most favorable one.•Presence of Ag ...clusters significantly red-shifts the absorption spectrum of Ptr.•SERS detection has potential benefits in both acidic and alkaline pH.
Metal nanoclusters (NCs) are widely present today in biosensing, bioimaging, and diagnostics due to their small size, great biocompatibility, and sensitivity to the biomolecular environment. Silver (Ag) NCs often possess intense fluorescence, photostability, and low photobleaching, which is in high demand during the detection of organic molecules. Pterins are small compounds, which are used in medicine as biomarkers of oxidative stress, cardiovascular diseases, neurotransmitter synthesis, inflammation and immune system activation. It is experimentally possible to detect pterin (Ptr) through the adsorption on Ag colloid. We optimized geometries and evaluated the binding energy in Ptr-Agnq complexes (n = 1–6; q = 0, +1, +2) using quantum chemistry methods. Different Ptr atoms were preferential for silver attachment depending on NC charge and size. The highest Eb was obtained for the complexes between the Ptr0 and Ag32+ (-50.8 kcal mol−1), between Ptr-1 and Ag32+ (-64.8 kcal mol−1), which means that these complexes should be formed preferably in aqueous solutions in acidic and alkaline media, respectively. The colorimetric detection of pterin with silver clusters does not seem to be promising. However, intense S0→S1 transitions of Ag5+ complexes look promising for luminescent Ptr detection. SERS detection of pterin is better to be done at pH > 8 since deprotonated pterin Raman undergo more dramatic changes upon addition of Ag than the neutral pterin. The characteristics of absorption and vibrational spectra of silver-pterin should be exploited during biosensor development.
Vitiligo is a type of hypomelanosis. Tetrahydrobiopterin (H4Bip), the coenzyme of the initial stage of melanogenesis, appears to be a trigger for vitiligo. H4Bip is present in vitiligo in 3–5-fold ...excess and causes oxidative stress by triggering an autocatalytic cycle of excess hydrogen peroxide synthesis. Using quantum-chemical calculations, we have evaluated the possibility of H4Bip reactions occurring in the dark and under ultraviolet (UV) irradiation, including the formation of dihydropterin dimers. In order to simulate the oxidative stress, oxidative modification of human serum albumin (HSA) has been carried out in the presence of excessive H4Bip using the fluorescence method. The fraction of oxidized protein (FOP) has been calculated. It has been established that there is a strong oxidative modification of amino acids chromophores (tryptophan and tyrosine) in the protein (FOP 0.64). Under UV irradiation of the system (HSA + H4Bip), FOP is reduced to 0.39. Apparently, a part of H4Bip transforms into dihydropterin dimers and does not participate in the oxidative modification of the protein. The data on oxidative modification of HSA are consistent with dynamic light scattering: H4Bip promotes HSA aggregation with the formation of particles with a hydrodynamic radius Rh ≥ 2000 nm, which can become immunogenic.
Pterins are an inseparable part of living organisms. Pterins participate in metabolic reactions mostly as tetrahydropterins. Dihydropterins are usually intermediates of these reactions, whereas ...oxidized pterins can be biomarkers of diseases. In this review, we analyze the available data on the quantum chemistry of unconjugated pterins as well as their photonics. This gives a comprehensive overview about the electronic structure of pterins and offers some benefits for biomedicine applications: (1) one can affect the enzymatic reactions of aromatic amino acid hydroxylases, NO synthases, and alkylglycerol monooxygenase through UV irradiation of H
pterins since UV provokes electron donor reactions of H
pterins; (2) the emission properties of H
pterins and oxidized pterins can be used in fluorescence diagnostics; (3) two-photon absorption (TPA) should be used in such pterin-related infrared therapy because single-photon absorption in the UV range is inefficient and scatters in vivo; (4) one can affect pathogen organisms through TPA excitation of H
pterin cofactors, such as the molybdenum cofactor, leading to its detachment from proteins and subsequent oxidation; (5) metal nanostructures can be used for the UV-vis, fluorescence, and Raman spectroscopy detection of pterin biomarkers. Therefore, we investigated both the biochemistry and physical chemistry of pterins and suggested some potential prospects for pterin-related biomedicine.
We have studied the excited states and structural properties for the complexes of cytosine (dC)10 chains with silver ions (Ag+) in a wide range of the Ag+ to DNA ratio (r) and pH conditions using ...circular dichroism, steady-state absorption, and fluorescence spectroscopy along with the ultrafast fluorescence upconversion technique. We also calculated vertical electronic transition energies and determined the nature of the corresponding excited states in some models of the cytosine–Ag+ complexes. We show that (dC)10 chains in the presence of silver ions form a duplex stabilized by C–Ag+–C bonds. It is also shown that the i-motif structure formed by (dC)10 chains is destabilized in the presence of Ag+ ions. The excited-state properties in the studied complexes depend on the amount of binding ions and the binding sites, which is supported by the calculations. In particular, new low-lying excited states appear when the second Ag+ ion interacts with the O atom of cytosine in the C–Ag+–C pairs. A similar picture is observed in the case when one Ag+ ion interacts with one cytosine via the N7 atom.
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