Pub Date : 2023-05-26DOI: 10.33435/tcandtc.1191117
Ayşe Hümeyra Taşkın Kafa, Rukiye Aslan, Hanaou Ahamada, B. Atron
Biofilm-associated infections are characterized by the chronicity, recurrence, and the requirement of a prolonged administration of multiple drugs. Several non-pathogenic and pathogenic species of microorganism including Mycobacteria spp form biofilm. Mycobacterial biofilms present a unique composition. Instead of exopolysaccharides in other bacteria, proteins are essential compounds of the biofilm matrix in mycobacteria. To tackle mycobacterial infections, a detailed understanding of the biofilm-forming mechanisms is crucial. In this present study, all available Mycobacterial proteins involved in the biofilm were selected. Their sequences were retrieved and characterized through the determination of their physicochemical properties, secondary structure, 3D structure, subcellular localization, conserved domain, ubiquitination sites, and virulence potentiality. Furthermore, druggability testing was undertaken after excluding proteins with homology to human proteins to identify possible drug targets. The results showed that they possess functionally important domains and families. All of the selected hypothetical proteins were stable. Six of them were classified as soluble and the remaining as transmembrane proteins. A sole protein was found to lack ubiquitination sites. Additionally, three of these were discovered to be virulent. Moreover, host non-homology results indicated eight pathogen-specific proteins that might be potential therapeutic targets. Among them, D-alanyl-D-alanine carboxypeptidase is a druggable target that is inhibited by beta-lactam antibiotics. The remainder of the proteins were categorized as new targets. In conclusion, this study may increase our knowledge of pathogenesis and host adaptation, drug resistance, and identification of drug and vaccine targets against infections caused by Mycobacteria. It can also guide new research.
生物膜相关感染的特点是慢性、复发，需要长期服用多种药物。包括分枝杆菌在内的几种非致病性和致病性微生物形成生物膜。分枝杆菌生物膜呈现出独特的组成。在分枝杆菌中，蛋白质是生物膜基质的基本化合物，而不是其他细菌中的外多糖。为了解决分枝杆菌感染，详细了解生物膜形成机制是至关重要的。在本研究中，我们选择了所有参与生物膜的分枝杆菌蛋白。通过测定它们的理化性质、二级结构、三维结构、亚细胞定位、保守结构域、泛素化位点和毒力潜力，对它们的序列进行了检索和表征。此外，在排除与人类蛋白同源的蛋白后，进行了药物性测试，以确定可能的药物靶点。结果表明，它们具有重要的功能域和家族。所有选择的假设蛋白质都是稳定的。其中6种可溶蛋白，其余为跨膜蛋白。唯一的蛋白被发现缺乏泛素化位点。此外，其中三种被发现是有毒的。此外，宿主非同源性结果表明，8种病原体特异性蛋白可能是潜在的治疗靶点。其中，d -丙氨酰- d -丙氨酸羧肽酶是可被β -内酰胺类抗生素抑制的药物靶点。其余的蛋白质被归类为新的靶标。总之，本研究可能增加我们对分枝杆菌的发病机制和宿主适应、耐药性以及针对分枝杆菌感染的药物和疫苗靶点的认识。它还可以指导新的研究。
{"title":"Structural and Functional Characterization of Biofilm-Related Proteins of Mycobacterium spp: An in-silico Approach","authors":"Ayşe Hümeyra Taşkın Kafa, Rukiye Aslan, Hanaou Ahamada, B. Atron","doi":"10.33435/tcandtc.1191117","DOIUrl":"https://doi.org/10.33435/tcandtc.1191117","url":null,"abstract":"Biofilm-associated infections are characterized by the chronicity, recurrence, and the requirement of a prolonged administration of multiple drugs. Several non-pathogenic and pathogenic species of microorganism including Mycobacteria spp form biofilm. Mycobacterial biofilms present a unique composition. Instead of exopolysaccharides in other bacteria, proteins are essential compounds of the biofilm matrix in mycobacteria. To tackle mycobacterial infections, a detailed understanding of the biofilm-forming mechanisms is crucial. In this present study, all available Mycobacterial proteins involved in the biofilm were selected. Their sequences were retrieved and characterized through the determination of their physicochemical properties, secondary structure, 3D structure, subcellular localization, conserved domain, ubiquitination sites, and virulence potentiality. Furthermore, druggability testing was undertaken after excluding proteins with homology to human proteins to identify possible drug targets. The results showed that they possess functionally important domains and families. All of the selected hypothetical proteins were stable. Six of them were classified as soluble and the remaining as transmembrane proteins. A sole protein was found to lack ubiquitination sites. Additionally, three of these were discovered to be virulent. Moreover, host non-homology results indicated eight pathogen-specific proteins that might be potential therapeutic targets. Among them, D-alanyl-D-alanine carboxypeptidase is a druggable target that is inhibited by beta-lactam antibiotics. The remainder of the proteins were categorized as new targets. \u0000In conclusion, this study may increase our knowledge of pathogenesis and host adaptation, drug resistance, and identification of drug and vaccine targets against infections caused by Mycobacteria. It can also guide new research.","PeriodicalId":36025,"journal":{"name":"Turkish Computational and Theoretical Chemistry","volume":"86 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73316775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-15DOI: 10.33435/tcandtc.1181765
Leila Hojatkashani̇, Amir Ali Omi̇di̇
DNA strands are essential in a cell for growth, metabolism regulation and carrying genetic information bases to new generations, in every creatures . The function of DNA bases is a 0 and 1 system. In this theoretical research , we try to make two other 0 and 1 systems for DNA bases .In both methods, C2Fe+ is attached to DNA bases and nucleotides like a flag to make derivatives. In the first method NMR susceptibility and Magnetization of pristine DNA bases, nucleotides and their C2Fe varieties are determined theoretically by using Gauss view and Gaussian programs. With effect of a magnetic field (H) and NMR susceptibility of these compounds, their calculate magnetizations , certain signals can be created as a mark of DNA bases and their compounds. These resulted not only can be considered as a method to make a new (0) and (1) system. In the second method, by using Gauss view and Gaussian programs the theoretically UV-Visible spectrum of pristine DNA bases, nucleotides and their C2Fe varieties are determined which the spectrum absorption of the pristine compounds are in different range with the absorption range of C2Fe varieties. With a little change in spectrophotometer construction another 0 and 1 coding system can be created, again.
{"title":"Theoretical Methods for coding a strand of DNA bases and nucleotides with C2Fe+, A DFT study","authors":"Leila Hojatkashani̇, Amir Ali Omi̇di̇","doi":"10.33435/tcandtc.1181765","DOIUrl":"https://doi.org/10.33435/tcandtc.1181765","url":null,"abstract":"DNA strands are essential in a cell for growth, metabolism regulation and carrying genetic information bases to new generations, in every creatures . The function of DNA bases is a 0 and 1 system. In this theoretical research , we try to make two other 0 and 1 systems for DNA bases .In both methods, C2Fe+ is attached to DNA bases and nucleotides like a flag to make derivatives. In the first method NMR susceptibility and Magnetization of pristine DNA bases, nucleotides and their C2Fe varieties are determined theoretically by using Gauss view and Gaussian programs. With effect of a magnetic field (H) and NMR susceptibility of these compounds, their calculate magnetizations , certain signals can be created as a mark of DNA bases and their compounds. These resulted not only can be considered as a method to make a new (0) and (1) system. In the second method, by using Gauss view and Gaussian programs the theoretically UV-Visible spectrum of pristine DNA bases, nucleotides and their C2Fe varieties are determined which the spectrum absorption of the pristine compounds are in different range with the absorption range of C2Fe varieties. With a little change in spectrophotometer construction another 0 and 1 coding system can be created, again.","PeriodicalId":36025,"journal":{"name":"Turkish Computational and Theoretical Chemistry","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74270141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-15DOI: 10.33435/tcandtc.1144794
Boulanouar Messaoudi, M. Cheriet, Rayenne Djemil, D. Khatmi̇
We have explored the potential energy surface of the triplet oxygen atom O(3P) reaction with 1,3-butadiene at CBS-QB3 levels of theory. Possible different pathways have been determined to better understand the reaction mechanism. Thus, the first pathway of the oxidation of 1,3-butadiene by the triplet oxygen O(3P) is show that the major product is CH3-CO-CH=CH2. The results agree with those obtained experimentally in relative to the reaction enthalpies. The transition state theory (TST) was employed to compute rate constants over the temperature range 297-798K. The obtained results have shown that the electrophilic O-addition pathways on the double bond are dominant up in the temperature range. The activation energy is in line with the proposed addition mechanism.
{"title":"Quantum investigation of the reaction between triplet oxygen O(3P) atom and butadiene","authors":"Boulanouar Messaoudi, M. Cheriet, Rayenne Djemil, D. Khatmi̇","doi":"10.33435/tcandtc.1144794","DOIUrl":"https://doi.org/10.33435/tcandtc.1144794","url":null,"abstract":"We have explored the potential energy surface of the triplet oxygen atom O(3P) reaction with 1,3-butadiene at CBS-QB3 levels of theory. Possible different pathways have been determined to better understand the reaction mechanism. Thus, the first pathway of the oxidation of 1,3-butadiene by the triplet oxygen O(3P) is show that the major product is CH3-CO-CH=CH2. The results agree with those obtained experimentally in relative to the reaction enthalpies. The transition state theory (TST) was employed to compute rate constants over the temperature range 297-798K. The obtained results have shown that the electrophilic O-addition pathways on the double bond are dominant up in the temperature range. The activation energy is in line with the proposed addition mechanism.","PeriodicalId":36025,"journal":{"name":"Turkish Computational and Theoretical Chemistry","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74508110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-15DOI: 10.33435/tcandtc.1181299
Rustaman Rustaman, Rizky RAFİ RAHMAWAN, I. Maksum
Diabetes Mellitus (DM) is characterized by increased blood glucose levels. It is generally caused by the pancreas' inability to produce insulin due to cell damage or insulin resistance. Due to the inhibition of adenosine triphosphate (ATP) production, which is essential for insulin secretion, one clinical pathology of this complication is insulin secretion dysfunction. Common methods of blood sugar diagnostics cannot distinguish mitochondrial diabetes and can lead to medication errors. Furthermore, an approach was developed through ATP biomarkers using an electrochemical biosensor with the help of an aptamer. However, it remains unknown precisely how and where the molecular interactions between the modified aptamer and ATP occur. Simulations were conducted in this study for 100 ns in silico using the amber18 computer program to determine the stability of the interaction and specificity between aptamer-ATP were compared to ADP and AMP. The results showed that the significant interactions are three hydrogen bonds between ATP and G7, G8, and A24. It was discovered that the aptamer-ATP complex had moderately good interaction and better potential for specificity than ADP and AMP. According to the RMSD, RMSF, and binding energy profiles, the system is still searching for the best conformation, necessitating a longer simulation time and additional studies to optimize the system. As a result, the system can reach a stable state and determine a more accurate energy calculation, hence, it is interpreted according to real applications.
{"title":"IN SILICO STUDY OF APTAMER SPECIFICITY FOR DETECTION OF ADENOSINE TRIPHOSPHATE (ATP) AS BIOSENSOR DEVELOPMENT FOR MITOCHONDRIA DIABETES DIAGNOSIS","authors":"Rustaman Rustaman, Rizky RAFİ RAHMAWAN, I. Maksum","doi":"10.33435/tcandtc.1181299","DOIUrl":"https://doi.org/10.33435/tcandtc.1181299","url":null,"abstract":"Diabetes Mellitus (DM) is characterized by increased blood glucose levels. It is generally caused by the pancreas' inability to produce insulin due to cell damage or insulin resistance. Due to the inhibition of adenosine triphosphate (ATP) production, which is essential for insulin secretion, one clinical pathology of this complication is insulin secretion dysfunction. Common methods of blood sugar diagnostics cannot distinguish mitochondrial diabetes and can lead to medication errors. Furthermore, an approach was developed through ATP biomarkers using an electrochemical biosensor with the help of an aptamer. However, it remains unknown precisely how and where the molecular interactions between the modified aptamer and ATP occur. Simulations were conducted in this study for 100 ns in silico using the amber18 computer program to determine the stability of the interaction and specificity between aptamer-ATP were compared to ADP and AMP. The results showed that the significant interactions are three hydrogen bonds between ATP and G7, G8, and A24. It was discovered that the aptamer-ATP complex had moderately good interaction and better potential for specificity than ADP and AMP. According to the RMSD, RMSF, and binding energy profiles, the system is still searching for the best conformation, necessitating a longer simulation time and additional studies to optimize the system. As a result, the system can reach a stable state and determine a more accurate energy calculation, hence, it is interpreted according to real applications.","PeriodicalId":36025,"journal":{"name":"Turkish Computational and Theoretical Chemistry","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89243208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-15DOI: 10.33435/tcandtc.1151841
T. Ertan-Bolelli, K. Bolelli, C. Altunayar‐Unsalan, Ozan Ünsalan, Bergüzar Yilmaz
Public health is still under attack by a worldwide pandemic caused by a coronavirus which is known to cause mainly respiratory and enteric disease in humans. Currently, still limited knowledge exists on the exact action mechanism and biology of SARS‒CoV‒2 although there are several effective vaccines and antiviral treatment. Besides, there is a considerable amount of 3D protein structures for SARS–CoV–2, related to its main protease resolved by X–ray diffraction. Here, we used molecular docking strategy to predict possible inhibitory activities of flavonoids on SARS–CoV–2 Mpro enzyme. For this, 800 flavonoids were retrieved from the ZINC database. Results suggested that avicularin was the lead flavonoid which docked to Mpro with the best binding energy. However, most of flavonoids showed H–bond interactions with Hie–41 and Cys–145 catalytic dyad, which were important residues for the catalytic activity of SARS–CoV–2 Mpro. Strong hydrogen bonding (2.36 Å) with Sγ atom of Cys145 residue was observed. This might suggest an initial formation of covalent bonding. Findings showed that selected flavonoids could be promising inhibitors of this enzyme and have the potential for future therapeutic drugs against COVID–19 after immediate experimental validation and clinical approvals.
{"title":"Effects of flavonoids on SARS–CoV–2 main protease (6W63): A molecular docking study","authors":"T. Ertan-Bolelli, K. Bolelli, C. Altunayar‐Unsalan, Ozan Ünsalan, Bergüzar Yilmaz","doi":"10.33435/tcandtc.1151841","DOIUrl":"https://doi.org/10.33435/tcandtc.1151841","url":null,"abstract":"Public health is still under attack by a worldwide pandemic caused by a coronavirus which is known to cause mainly respiratory and enteric disease in humans. Currently, still limited knowledge exists on the exact action mechanism and biology of SARS‒CoV‒2 although there are several effective vaccines and antiviral treatment. Besides, there is a considerable amount of 3D protein structures for SARS–CoV–2, related to its main protease resolved by X–ray diffraction. Here, we used molecular docking strategy to predict possible inhibitory activities of flavonoids on SARS–CoV–2 Mpro enzyme. For this, 800 flavonoids were retrieved from the ZINC database. Results suggested that avicularin was the lead flavonoid which docked to Mpro with the best binding energy. However, most of flavonoids showed H–bond interactions with Hie–41 and Cys–145 catalytic dyad, which were important residues for the catalytic activity of SARS–CoV–2 Mpro. Strong hydrogen bonding (2.36 Å) with Sγ atom of Cys145 residue was observed. This might suggest an initial formation of covalent bonding. Findings showed that selected flavonoids could be promising inhibitors of this enzyme and have the potential for future therapeutic drugs against COVID–19 after immediate experimental validation and clinical approvals.","PeriodicalId":36025,"journal":{"name":"Turkish Computational and Theoretical Chemistry","volume":"184 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73961098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-15DOI: 10.33435/tcandtc.1161253
Idrees Orei̇bi̇, Jassim M. AL-ISSAWE
The electronic and optical properties of the WSeTe monolayer have already been evaluated at different hydrostatic pressures up to 9 GPa using a first principles simulation based on dft. At all pressures, the material is semi-conductive and the band gap narrows. The examination of optical functions demonstrates that the WSeTe monolayer's absorption increases significantly as we travel towards the violet region as well as conductivity, making it useful in solar cells. All optical qualities increase as a result of the applied pressure. We contend that the extraordinary photovoltaic properties of the WSeTe monolayer have many applications in optical devices.
{"title":"A class of two-dimensional WSeTe monolayers under pressures with novel electronic and optical properties","authors":"Idrees Orei̇bi̇, Jassim M. AL-ISSAWE","doi":"10.33435/tcandtc.1161253","DOIUrl":"https://doi.org/10.33435/tcandtc.1161253","url":null,"abstract":"The electronic and optical properties of the WSeTe monolayer have already been evaluated at different hydrostatic pressures up to 9 GPa using a first principles simulation based on dft. At all pressures, the material is semi-conductive and the band gap narrows. The examination of optical functions demonstrates that the WSeTe monolayer's absorption increases significantly as we travel towards the violet region as well as conductivity, making it useful in solar cells. All optical qualities increase as a result of the applied pressure. We contend that the extraordinary photovoltaic properties of the WSeTe monolayer have many applications in optical devices.","PeriodicalId":36025,"journal":{"name":"Turkish Computational and Theoretical Chemistry","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90560413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-28DOI: 10.33435/tcandtc.1206061
Ahmad NAZİB ALİAS, Zubainun MOHAMED ZABİDİ, A. Ali̇
Poly(N-vinylcarbazole) has been widely used in polymer light emitting diodes due to its unique electronic properties. The electronic properties of Poly(N-vinylcarbazole) were examined using the Semi-Empirical Zerner Modified Intermediate Neglect of Differential Overlap (ZINDO) oligomer extrapolation method. In this calculation, the electronic properties of Poly(N-vinylcarbazole) were extracted from oligomer electronic properties. We identified a tendency for oligomers with large HOMO-LUMO gaps in the form of linear regression as function of reciporocal of monomeric units. The increasing number of monomers induce the interaction between energy levels of each monomer which boardening the energy levels. The localized molecular orbital and vibration spectra of the basic unit of polymer Poly(N-vinylcarbazole) also has been investigated.
{"title":"Electronic Properties of Poly(N-vinylcarbazole) Using semi-empirical oligomer extrapolation approximations","authors":"Ahmad NAZİB ALİAS, Zubainun MOHAMED ZABİDİ, A. Ali̇","doi":"10.33435/tcandtc.1206061","DOIUrl":"https://doi.org/10.33435/tcandtc.1206061","url":null,"abstract":"Poly(N-vinylcarbazole) has been widely used in polymer light emitting diodes due to its unique electronic properties. The electronic properties of Poly(N-vinylcarbazole) were examined using the Semi-Empirical Zerner Modified Intermediate Neglect of Differential Overlap (ZINDO) oligomer extrapolation method. In this calculation, the electronic properties of Poly(N-vinylcarbazole) were extracted from oligomer electronic properties. We identified a tendency for oligomers with large HOMO-LUMO gaps in the form of linear regression as function of reciporocal of monomeric units. The increasing number of monomers induce the interaction between energy levels of each monomer which boardening the energy levels. The localized molecular orbital and vibration spectra of the basic unit of polymer Poly(N-vinylcarbazole) also has been investigated.","PeriodicalId":36025,"journal":{"name":"Turkish Computational and Theoretical Chemistry","volume":"64 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83902624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-15DOI: 10.33435/tcandtc.1102295
Anaridha S., Mohamed IMRAN P K, Khaja MOHİDEEN A, Salım MEERAN I, Shabeer T. K.
U.S. FDA approved anti-cancer drugs, namely ribociclib and copanlisib used for treating breast cancer and follicular lymphoma, respectively, were chosen for computational study. Quantum chemical calculations via DFT and MP2 were used for energy optimization of the drugs. Chemical descriptor parameters were compared between DFT and MP2 values for each atom, and the most reactive and stable atoms were reported. To describe the reactivity and stability of the drug molecules, Fukui functions were calculated. Molecular docking of the drugs was performed against epidermal growth factor receptor (EGFR) and cellular inhibitor of apoptosis protein-1 (cIAP1) receptor proteins to study the drug-protein binding interactions. The binding energy values before optimization and after optimization were found to be -11.21 and -14.41 kcal.mol-1 for copanlisib and -13.58 kcal and -29.08 kcal for ribociclib respectively. Atoms O27 and O10 are reported to be the most reactive atom based on high softness value. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the drugs were evaluated using open-source in-silico tools. ADME profiling of drug molecules indicated good to moderate solubility and low to high absorption in the gastrointestinal tract. Predicted toxicity was class five for both anti-cancer drugs. The structural and bioactive properties of the drugs focused on in this study help evaluate the better reactivity patterns of anticancer medicines.
{"title":"Computational analysis using ADMET profiling, DFT calculations and molecular docking of two anti-cancer drugs","authors":"Anaridha S., Mohamed IMRAN P K, Khaja MOHİDEEN A, Salım MEERAN I, Shabeer T. K.","doi":"10.33435/tcandtc.1102295","DOIUrl":"https://doi.org/10.33435/tcandtc.1102295","url":null,"abstract":"U.S. FDA approved anti-cancer drugs, namely ribociclib and copanlisib used for treating breast cancer and follicular lymphoma, respectively, were chosen for computational study. Quantum chemical calculations via DFT and MP2 were used for energy optimization of the drugs. Chemical descriptor parameters were compared between DFT and MP2 values for each atom, and the most reactive and stable atoms were reported. To describe the reactivity and stability of the drug molecules, Fukui functions were calculated. Molecular docking of the drugs was performed against epidermal growth factor receptor (EGFR) and cellular inhibitor of apoptosis protein-1 (cIAP1) receptor proteins to study the drug-protein binding interactions. The binding energy values before optimization and after optimization were found to be -11.21 and -14.41 kcal.mol-1 for copanlisib and -13.58 kcal and -29.08 kcal for ribociclib respectively. Atoms O27 and O10 are reported to be the most reactive atom based on high softness value. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the drugs were evaluated using open-source in-silico tools. ADME profiling of drug molecules indicated good to moderate solubility and low to high absorption in the gastrointestinal tract. Predicted toxicity was class five for both anti-cancer drugs. The structural and bioactive properties of the drugs focused on in this study help evaluate the better reactivity patterns of anticancer medicines.","PeriodicalId":36025,"journal":{"name":"Turkish Computational and Theoretical Chemistry","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80325477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-15DOI: 10.33435/tcandtc.1121985
M. Yaşar, Ekrem Yaşar, Nuri Yorulmaz, Emin Tenekeci̇, İ. Sarpün, E. Eroglu
Possible allosteric inhibitors of MPro were investigated using in silico methods. To this end, FDA-approved drugs in the DrugBank database were subjected to virtual screening, and drugs that strongly bind distant from the catalytic site of MPro were identified using molecular docking. Among the identified drugs, Dihydroergotamine (DHE) was chosen for further investigation due to its highest binding score against MPro in the molecular docking experiment. The allosteric inhibition potential of DHE toward MPro was demonstrated by applying some computational tools on the trajectory files which were obtained from the Molecular Dynamics Simulations. Results support that the hydrogen bonding interactions of DHE with GLU278 and THR280, located between Protomer A and Protomer B, affect the structure of the side chain of CYS145 at the catalytic site of MPro. Considering the role of CYS145 in the catalytic cycle, this structural change is likely to be a mechanism for inhibiting MPro.
{"title":"An in silico investigation of allosteric inhibition potential of Dihydroergotamine against Sars-CoV-2 Main Protease (MPro)","authors":"M. Yaşar, Ekrem Yaşar, Nuri Yorulmaz, Emin Tenekeci̇, İ. Sarpün, E. Eroglu","doi":"10.33435/tcandtc.1121985","DOIUrl":"https://doi.org/10.33435/tcandtc.1121985","url":null,"abstract":"Possible allosteric inhibitors of MPro were investigated using in silico methods. To this end, FDA-approved drugs in the DrugBank database were subjected to virtual screening, and drugs that strongly bind distant from the catalytic site of MPro were identified using molecular docking. Among the identified drugs, Dihydroergotamine (DHE) was chosen for further investigation due to its highest binding score against MPro in the molecular docking experiment. The allosteric inhibition potential of DHE toward MPro was demonstrated by applying some computational tools on the trajectory files which were obtained from the Molecular Dynamics Simulations. Results support that the hydrogen bonding interactions of DHE with GLU278 and THR280, located between Protomer A and Protomer B, affect the structure of the side chain of CYS145 at the catalytic site of MPro. Considering the role of CYS145 in the catalytic cycle, this structural change is likely to be a mechanism for inhibiting MPro.","PeriodicalId":36025,"journal":{"name":"Turkish Computational and Theoretical Chemistry","volume":"39 9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80967142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.33435/tcandtc.1227137
Umar Farooque, Sandhir Kumar Si̇ngh, Tarique Rashid, Md. Iftekhar Alam
Simple analytical models for the calculation of concentration (c) and temperature (T) dependent refractive index i.e., n(c,T) values of the six solutions namely, three electrolyte (KCl, NaCl, and CaCl2), a polar (glucose), a non-polar (ethyl acetate), and a protein (bovine serum albumin) solutions have been proposed. The values of refractive index obtained using our proposed models have been compared with the corresponding values of the refractive index obtained using other reported models and the experimental values. A fairly good agreement between them has been obtained.
{"title":"Simple model for the calculation of concentration and temperature dependent refractive index of different solutions","authors":"Umar Farooque, Sandhir Kumar Si̇ngh, Tarique Rashid, Md. Iftekhar Alam","doi":"10.33435/tcandtc.1227137","DOIUrl":"https://doi.org/10.33435/tcandtc.1227137","url":null,"abstract":"Simple analytical models for the calculation of concentration (c) and temperature (T) dependent refractive index i.e., n(c,T) values of the six solutions namely, three electrolyte (KCl, NaCl, and CaCl2), a polar (glucose), a non-polar (ethyl acetate), and a protein (bovine serum albumin) solutions have been proposed. The values of refractive index obtained using our proposed models have been compared with the corresponding values of the refractive index obtained using other reported models and the experimental values. A fairly good agreement between them has been obtained.","PeriodicalId":36025,"journal":{"name":"Turkish Computational and Theoretical Chemistry","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86304642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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