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The Klopman-Peradejordi-Gómez (KPG) method relates the variation of the numerical values of a biological activity, measured in vivo or in vitro, with the variation of the numerical values of a set of local atomic reactivity and orientational parameters of the substituents indices belonging to a certain skeleton, defined as a set of atoms common to...
Citations
... Pi-alkyl interactions occur in the pi electron cloud with an aromatic group and electron groups of several alkyl groups. Pi-alkyl interactions occur when the centroid of the pi ring and the alkyl group are inside the alkyl centroid and have at least a pair of nearest atoms with similar pi-pi [57]. ...
The salivary glands of mosquitoes contain protein molecules that facilitate blood-feeding. One important protein in Aedes aegypti ( Ae. aegypti ) salivary glands is the D7 protein, which is known to inhibit platelet aggregation by binding to leukotriene A4 molecules upon blood-feeding. Leukotriene A 4 is known as a molecule that improves platelet aggregation. This ability to bind to leukotriene A4 demonstrates the potential of a new thrombolytic agent. This can be investigated through an in-silico study using the molecular docking method. The present study involved the 3D structure of the D7 protein and the Leukotriene A4 ligand. It also comprised preparing their structures, validating the molecular docking method, and analyzing the outcomes. The result of the molecular docking documented an ΔG value of 6.63 kcal/mol, which signified stable and spontaneous binding between the D7 protein and the leukotriene A 4 . The active site of the D7 protein when binding to the leukotriene A4 ligand involves several amino acid residues, namely GLN 177, TYR 178, ARG 176, VAL 193, ILE 175, MET 194, PHE 154, PHE 186, HIS 189, TYR 248 and PHE 264. The ability to bind to leukotriene A 4 , as an inducer of platelet aggregation, evidences the potential as a novel thrombolytic agent.
... Another possibility is to fully localize the molecular (HOMO) and (HOMO-1) on atom 9. Thus, atom 9 seems to interact with an electron-deficient center (π-cation or π-π interactions). Another possibility is that π electrons of atom 9 participate in a N9-H22-O hydrogen bond 37 . Atom 20 is a hydrogen atom bonded to N12 in the chain linking rings B and C (Fig. 8). ...
... This is consistent with the second tactic just mentioned. The first tactic further suggests that atom 13 could be interacting with an electron-deficient site (alkyl or CH-π interactions 37 ). Atom 14 is a sp2 carbon atom in ring C (Fig. 8). ...
... Therefore, atom 23 should be interacting with an electron-rich center at least in the case of an H atom. We suggest that in this case a carbon H-bond could occur (this suggestion is made despite the fact that in the definition of a carbon hydrogen bond it is stated that "a carbon atom is considered a donor either if it is in an acetylene group or if it is adjacent to an oxygen or nitrogen atom") 37 . Another possibility is that the empty σ MOs of atom 23 interact weakly with the occupied MOs of the site. ...
... between a π ring that functions as a hydrogen bond acceptor and a hydrogen bond donor atom (Gómez, et al., 2020). Another type interaction in this research was hydrophobic Interaction that divide into 2 types, alkyl interactions and π-alkyl interactions. ...
... Unfavorable Bonds donor is connected to a non-aromatic carbon atom and meets the appropriate distance and relative position requirements (Gómez, et al., 2020). ...
... Different types of unfavorable interactions can happen between atoms, such as steric bumps, which happen when the distance between atoms is less than a certain threshold, repulsive charge interactions between atoms with the same charge, acceptor-acceptor clashes when two acceptor atoms are too close, donor-donor clashes between two donor atoms, and metal repulsion between a metal ion and a donor atom. Factors like distance, charge, and the presence of certain atoms can cause these interactions (Gómez, et al., 2020). ...
Human epidermal growth factor receptor-2 (HER-2) is an essential oncogene in breast cancer. HER-2 causes 25% of breast cancer, and this type of cancer tends to grow and spread faster than others but had a good response to HER-2 targeted therapy. This study aims to analyze chemical compounds in saffron plants (Crocus sativus) that potential to breast anticancer activity by inhibiting HER-2 receptor (PDB ID: 3RCD). The study employed in silico research such as molecular docking using AutoDock Tools software, and visualization with Biovia Discovery Studio. In addition, molecular dynamic simulation was conducted using GROMACS software, with visualization performed using Grace. The molecular docking results showed that Crocetin has a lower binding energy value of -8.37 kcal/mol compared to Herceptin, which is -7.11 kcal/mol and the lowest energy among Saffron bioactive compounds. These results indicated that the affinity of Crocetin in binding to HER-2 receptor is better than Herceptin. The molecular interactions were hydrogen, hydrophobic, electrostatic, and unfavorable bonds. The MD results showed that the RMSD value meets the 0.2-0.5 nm stability requirements. According to the data analysis, Herceptin appears to have a more stable RMSF value when compares to Crocetin. The Rg graph of both complexes showed stability until the end of the simulation. The H-bond results show that the Herceptin complex has more hydrogen bonds than the Crocetin complex. These results showed that the chemical components of saffron plants have the potential as breast anticancers by inhibiting the HER-2 receptor.Keywords: anticancer, Crocus sativus, HER-2 receptor, molecular docking, molecular dynamic.
... To comprehend a mechanism of action, researchers can examine the relationships between the descriptors of the QSAR model and toxicity or other activities [21]. The assumption that the molecular structure of a series of compounds contains essential information about the factors responsible for their physical, chemical, or biological properties has led chemoinformaticians to extensively employ QSAR/QSPR to study the biological activity of various compounds [19,[22][23][24][25][26][27]. Presently, one of the greatest challenges in QSAR/QSPR studies is assessing the reliability of the mechanistic interpretation of the identified relationships [28]. ...
Bacillus subtilis is a bacterium that has demonstrated its efficacy across various domains, including industry, agriculture, and commerce, owing to its protective, inhibitory, and biological mechanisms against specific microbes. However, at high concentrations, it can lead to food poisoning and severe infections, resulting in symptoms such as diarrhea and vomiting. Bacterial spores produced by Bacillus subtilis can induce conditions like gas gangrene and tetanus. In this context, benzohydrazones are recognized for their antimicrobial activity, particularly against Bacillus subtilis. This study aims to elucidate the relationship between the electronic structure of para-substituted benzaldehyde benzohydrazone derivatives and their antimicrobial activity. This leads to the proposal of a 2D pharmacophore for predicting the antibacterial activity of these derivatives. The quantitative structure-activity relationship (QSAR) approach employed is the KPG method. The electronic structures were optimized using the density functional theory (DFT) method with the B3LYP functional and the 6-31G (d,p) basis set. Charge and local molecular orbitals were considered in the optimization process. The resulting prediction equation (R=98.95%, R²=97.91%, Adjusted R²=96.76%, F(5,9)=84.52) derived from multiple linear regression provides the basis for the proposed 2D pharmacophore. This equation shows that antimicrobial activity of benzohydrazone derivative is on charge and orbital controlled. This pharmacophore holds potential utility in designing new molecular structures with enhanced activity against Bacillus subtilis.
... Senyawa pirazolo-piridin hanya dapat membentuk ikatan hidrogen karbon (C-H---O atau C-H---N) dengan asam amino His71, Phe594, dan Ser516. Namun, tentunya jenis ikatan hidrogen ini jauh lebih lemah dibandingkan dengan ikatan hidrogen konvensional (O-H---O) (Itoh et al., 2019;Gómez-Jeria et al., 2020). Selain itu, senyawa pirazolo-piridin juga dapat berinteraksi melalui interaksi van der Waals dan beberapa interaksi lain, sebagaimana dapat dilihat pada gambar 11. ...
Scaffold pirazol maupun piazolo-piridin telah dilaporkan memiliki potensi aktivitas biologis yang menarik dan terdapat pada berbagai struktur senyawa obat yang telah disetujui oleh food and drug administration (FDA). Pada penelitian ini, senyawa pirazolo-piridin tersubstitusi metoksi sebagai turunan dari analog kurkumin monokarbonil telah disintesis melalui dua tahap reaksi. Tahap pertama adalah sintesis analog kurkumin monokarbonil tersubsitusi metoksi melalui reaksi kondensasi Claisen-Schmidt dengan bantuan iradiasi microwave. Tahap kedua adalah sintesis senyawa pirazolo-piridin melalui reaksi adisi nukleofilik yang diikuti oleh reaksi siklisasi intramolekular dalam reaktor tertutup, monowave 50. Kemurnian produk hasil sintesis telah dipastikan melalui analisis HPLC. Struktur senyawa pyrazolo-piridin telah dikonfirmasi melalui analisis spektroskopi UV-Vis, FT-IR, dan 1H-NMR. Berdasarkan studi molecular docking, senyawa tersebut tidak menunjukkan potensi aktivitas yang baik sebagai inhibitor enzim siklooksigenase-2 (COX-2), karena hanya memiliki nilai energi bebas pengikatan sebesar -5,98 kcal/mol. Selain itu, pirazolo piridin tersubstitusi metoksi juga tidak dapat membentuk satupun ikatan hidrogen dengan sisi aktif COX-2. Di sisi lain, celecoxib sebagai kontrol positif memiliki energi bebas pengikatan sebesar -11,97 kcal/mol dan dapat membentuk empat ikatan hidrogen dengan Gln178, Leu338, Arg499, dan Phe504 pada sisi aktif COX-2 (PDB ID: 3LN1).
... We worked within the common skeleton concept: a definite collection of atoms common to all molecules analyzed accounting for about all the biological activity. Then, distinct parts or this common skeleton should account for almost all the interactions leading to the expression of a given biological activity [55]. The common skeleton for biphenyl ether derivatives is shown in Fig. 5. ...
The Klopman-Peradejordi-Gómez (KPG) QSAR method has been employed to search for formal relationships between herbicidal activity and electronic structure in a series of biphenyl ether derivatives having a five-membered heterocycle. Full geometry optimization and electronic structure calculations were performed within the Density Functional Theory at the B3LYP/6-311g(d,p) level with water as solvent (Polarizable Continuum Model). Three statistically significant relationships were found. The results of these three equations are completely compatible with each other. With that information, some drug-PPO interactions have been suggested. We analyzed the conformations of the optimized molecules as well as the conformers of the most and least active molecules. A qualitative analysis of the overlap of the molecules in their optimized form was also carried out for comparison purposes. Finally, the MEPs of the more active molecule were compared with those of the less active molecule at different distances from the nuclei. It is hoped that this information will be helpful to experimentalists. In particular, the conformers of molecule 21 offer an interesting possibility to develop new molecules.
... Hydrogen bonding is used as a comparison because it has a relatively stronger interaction (Xie et al., 2015). The hydrogen bonding data of all peptides in more detail is summarized in Table 3. Whereas, WF (Trp-Phe) had abundant interaction, however, none of them was unfavorable interaction, which occurs between the same sign, such as donor-donor bond, acceptor-acceptor, positive-positive, or steric effect, leading to the decrease in stability of the complex [49] [50]. ...
One of potential inhibitors which is widely used for the clinical treatment of COVID-19 in comorbid patients is Angiostensin Converting Enzyme-1 (ACE1) inhibitor. A safer peptide-based ACE1 inhibitor derived from salmon skin collagen, that is considered as the by-product of the fish processing industry have been investigated in this study. The inhibitory activity against ACE1 was examined using in vitro and in silico methods. In vitro analysis includes the extraction of acid-soluble collagen, characterization using FTIR, Raman, UV–Vis, XRD, cytotoxicity assay, and determination of inhibition against ACE1. In silico method visualizes binding affinity, molecular interaction, and inhibition type of intact collagen and active peptides derived from collagen against ACE1 using molecular docking. The results of FTIR spectra detected amide functional groups (A, B, I, II, III) and imine proline/hydroxyproline, while the results of Raman displayed peak absorption of amide I, amide III, proline/hydroxyproline ring, phenylalanine, and protein backbone. Furthermore, UV–Vis spectra showed typical collagen absorption at 230 nm and based on XRD data, the chain types in the samples were α-helix. ACE1 inhibition activity was obtained in a concentration-dependent manner where the highest was 82.83% and 85.84% at concentrations of 1000, and 2000 µg/mL, respectively, and showed very low cytotoxicity at the concentration less than 1000 µg/mL. In silico study showed an interaction between ACE1 and collagen outside the active site with the affinity of − 213.89 kcal/mol. Furthermore, the active peptides of collagen displayed greater affinity compared to lisinopril, namely HF (His-Phe), WYT (Trp-Tyr-Thr), and WF (Trp-Phe) of − 11.52; − 10.22; − 9.58 kcal/mol, respectively. The salmon skin-derived collagen demonstrated ACE1 inhibition activity with a non-competitive inhibition mechanism. In contrast, the active peptides were predicted as potent competitive inhibitors against ACE1. This study indicated that valorization of fish by-product can lead to the production of a promising bioactive compound to treat COVID-19 patient with diabetic comorbid.
Graphical Abstract
... This is called the common skeleton. The number of atoms of this common skeleton defines the index Z of Eq. 1 [26]. The second mandatory condition is that we must have at least the same number of equations than the total number of indices of the common skeleton plus the other terms of Eq. 1. ...
... All this procedure will make C37 a very bad electron donor. For this reason, we suggest that this atom could be engaged in alkyl and/or alkyl-π interactions at a distance of about 5.5Å [26]. Atom 18 is a hydrogen atom attached to a sp 3 carbon atom C13 of the saturated ring C (Figs. 1 and 10). ...
... Tables 6 and 7 show the local molecular orbitals of atoms appearing in Eqn. 2 and 3. Figure 6 shows two views of the MEP map of molecule 5 at 4.5 Å of the nuclei [60]. 5Å it is theoretically possible to identify some areas of the MEP associated with non-bond interactions such as π-cation or π-anion ones, helping to discard or not some suggestions resulting from the analysis of the statistical equations [61]. We do not know works following this line of thought but, to achieve this goal, MEP maps at 6, 5.5, 5 and 4.5Å seem necessary. ...
... Therefore, what we want is to find the conditions to maximize this percentage. Discussion of the results for the percentage of inhibition of radioligand binding of test compounds at human A2A receptors [61,63]. Table 2 shows that the importance of variables in Eq. 2 is S12 E (HOMO)* F20(LUMO+1)* μ20 * > F25(HOMO)*>> F26(HOMO)* F25(HOMO-2)*> S15 N (LUMO+2)*. ...
Employing the Klopman-Peradejordi-Gómez formal method we have analyzed the relationships between the electronic structure and the percentage of inhibition of radioligand binding for the case of a group of 2-aryladenine derivatives interacting with the human A2A and A2B adenosine receptors. The ultimate goal is suggesting modifications of the structure of 2-aryladenine derivatives to enhance the percentage of inhibition of radioligand binding. All electronic structure calculations were carried out with the Gaussian set of programs and with software written in this Unit. For each case, we found statistically significant relationships. The equations relate the variation of the percentage of inhibition to the variation of the numerical values of a set of local atomic reactivity indices. These indices allowed us to propose possible atom-site non-bonded interactions that could serve as a basis for the development of new molecules with enhanced or diminished activities.
... An atom that is said to be a hydrogen bond acceptor must have at least 1 unpaired electron. This bond is strong so that it can increase the stability of the active enzymepeptide complex (Gómez-Jeria et al., 2020). An interaction is also possible between uncharged molecules, although, this interaction is weak and highly affected by the movement of electrons as the molecules approach each other. ...
... The T-shaped π-π interaction is almost similar to stacked π-π except that one ring is sideways and leads to the other ring, where this interaction was occurred between the TYR666 residue with WF (Trp-Phe), WG (Trp-Gly), and WY (Trp-Tyr) peptides. Stacked amides are formed due to the presence of an amide group and a π ring interacting with each other (Gómez-Jeria et al., 2020). Specifically, examples of this interaction are TYR666 residues with TF (Thr-Phe), VF (Val-Phe), and VW (Val-Trp) and SER630 residues with WG (Trp-Gly). ...
... Moreover, other molecular interactions were found in the active peptide complex with the DPP-IV include π-sulfur. The formation of this interaction was a result from the presence of sulfur atoms in amino acid residues or ligands which placed at a certain distance close to the π ring, for example in TYR631, TRP659, and TYR662 with RM (Arg-Met) (Gómez-Jeria et al., 2020). ...
Fish skin collagen hydrolyzate has demonstrated the potent inhibition of dipeptidyl peptidase-IV (DPP-IV), one of the treatments for type-2 diabetes mellitus (type-2 DM), but the precise mechanism is still unclear. This study used in silico method to evaluate the potential of the active peptides from tilapia skin collagen (Oreochromis niloticus) for DPP-IV inhibitor. The methodology includes collagen hydrolysis using BIOPEP, which is the database of bioactive peptides; active peptide selection; toxicity, allergenicity, sensory analysis of active peptides; and binding of active peptides to DPP-IV compared with linagliptin. The result indicated that in silico enzymatic hydrolysis of collagen produced active peptides with better prediction of biological activity than intact collagen. There are 13 active peptides were predicted as non-toxic and non-allergenic, some of which have a bitter, salty, and undetectable taste. Docking simulations showed all active peptides interacted with DPP-IV through hydrogen bonds, van der Waals forcehydrophobic interaction, electrostatic force, π-sulfur, and unfavorable interaction, where WF (Trp-Phe), VW (Val-Trp), WY (Trp-Tyr), and WG (Trp-Gly) displayed higher binding affinities of 0.8; 0.5; 0.4; and 0.3 kcal/mol compared with linagliptin. In this study, we successfully demonstrated antidiabetic type-2 DM potential of the active peptides from tilapia skin collagen. The obtained data provided preliminary data for further research in the utilization of fish skin waste as a functional compound to treat the type-2 DM patients. Alternatively, this treatment can be synergistically combined with the available antidiabetic drugs to improve the insulin secretion of the type-2 DM patients.
