Simulasi Penambatan Molekuler Senyawa Kompleks Besi Terhadap Protein Hemofor sebagai Kandidat Fotosensitizer pada Terapi Fotodinamika

al-Kimiya ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. 1-8
Author(s):  
Taufik Muhammad Fakih ◽  
Anggi Arumsari ◽  
Mentari Luthfika Dewi ◽  
Nurfadillah Hazar ◽  
Tanisa Maghfira Syarza
Keyword(s):  
Pseudomonas Aeruginosa ◽  
In Silico ◽  
Protein Docking ◽  
Autodock 4.2

Resistensi antibiotika muncul sebagai polemik yang dapat mempengaruhi kesehatan manusia. Kemajuan teknologi membuka peluang dalam penemuan molekul senyawa baru yang mampu mencegah perkembangan mikroba patogen, seperti Pseudomonas aeruginosa yang resisten terhadap beberapa jenis antibiotika. Terapi fotodinamika dengan memanfaatkan penggunaan fotosensitizer yang berasal dari senyawa yang membentuk kompleks dengan besi merupakan salah satu pendekatan alternatif untuk mengatasi penyakit infeksi dengan risiko resistensi mikroba yang lebih rendah. Penelitian yang dilakukan secara in silico ini bertujuan untuk mengamati, mengeksplorasi, dan mengevaluasi mekanisme aksi berbasis struktural dari molekul senyawa yang membentuk kompleks dengan besi, yaitu besi-ftalosianina dan besi-salofen terhadap protein hemofor HasAp serta pengaruh molekularnya terhadap bagian situs aktif pengikatan dari protein hemofor HasR. Identifikasi interaksi molekuler dan afinitas antara molekul senyawa besi-ftalosianina dan besi-salofen terhadap protein hemofor HasAp dilakukan dengan simulasi ligan-protein docking mempergunakan software MGLTools 1.5.6 yang dilengkapi dengan AutoDock 4.2. Di samping itu, dilakukan juga simulasi protein-protein docking terhadap sistem kompleks ligan-protein untuk memastikan pengaruh molekularnya terhadap bagian situs aktif pengikatan dari protein hemofor HasR dengan mempergunakan software PatchDock. Berdasarkan simulasi ligan-protein docking diperoleh hasil bahwa senyawa besi-ftalosianina memiliki afinitas paling baik terhadap kedua protein hemofor HasAp, dengan nilai energi bebas pengikatan masing-masing sebesar −68,45 kJ/mol dan −65,23 kJ/mol. Menariknya, hasil simulasi protein-protein docking antara kompleks molekul senyawa besi-ftalosianina dan protein hemofor HasAp-besi-ftalosianina terhadap protein hemofor HasR memiliki nilai energi kontak atom yang positif sebesar 556,56 kJ/mol. Dari penelitian ini dapat diprediksikan bahwa perbedaan struktur molekul senyawa yang membentuk kompleks dengan besi mampu mempengaruhi mekanisme aksi berbasis structural terhadap protein hemofor target.

scholarly journals Identifikasi Mekanisme Molekuler Senyawa Ftalosianina sebagai Kandidat Photosensitizer pada Terapi Fotodinamika secara In Silico

2021 ◽  
Vol 17 (1) ◽  
pp. 37
Author(s):  
Taufik Muhammad Fakih ◽  
Anggi Arumsari ◽  
Mentari Luthfika Dewi ◽  
Nurfadillah Hazar ◽  
Tanisa Maghfira Syarza
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Photodynamic Therapy ◽  
Mechanism Of Action ◽  
In Silico ◽  
Pathogenic Bacteria ◽  
Docking Study ◽  
Protein Docking ◽  
Atomic Contact ◽  
Study Results ◽  
Autodock 4.2

<p>Bakteri patogen seperti Pseudomonas aeruginosa membutuhkan zat besi untuk dapat mempertahankan kelangsungan hidupnya. HasAp merupakan suatu protein yang dihasilkan oleh bakteri patogen sebagai sumber zat besi tersebut. Protein HasAp selanjutnya akan berikatan dengan protein membran luar yaitu HasR untuk dapat meneruskan sinyal pada sel bakteri. Penyerapan zat besi pada bakteri patogen ini dapat menjadi strategi pengembangan metode terapi dalam mengendalikan dan mencegah penyakit infeksi yang disebabkan oleh bakteri patogen Pseudomonas aeruginosa, salah satunya dengan memanfaatkan ftalosianina sebagai photosensitizer pada terapi fotodinamika. Penelitian ini bertujuan untuk mengidentifikasi, mengevaluasi, dan mengeksplorasi mekanisme aksi senyawa ftalosianina terhadap protein HasAp, serta pengaruhnya pada bagian sisi aktif HasR dengan menggunakan studi <em>in silico</em>. Studi ligan-protein <em>docking </em>dilakukan dengan menggunakan perangkat lunak MGLTools 1.5.6 yang dilengkapi dengan AutoDock 4.2 untuk mengamati afinitas dan interaksi molekuler antara molekul senyawa Fe-ftalosianina (Fe-Pc) dan Ga-ftalosianina (Ga-Pc) terhadap makromolekul protein HasAp. Selanjutnya, studi protein-protein <em>docking</em> dilakukan terhadap sistem kompleks ligan-protein untuk mengamati pengaruhnya terhadap area pengikatan dari makromolekul protein HasR dengan menggunakan perangkat lunak PatchDock. Berdasarkan hasil ligan-protein <em>docking</em>, senyawa Fe-ftalosianina (Fe-Pc) memiliki afinitas paling baik terhadap kedua protein HasAp, yaitu dengan nilai masing-masing -68,45 kJ/mol dan -69,16 kJ/mol. Kemudian, hasil studi protein-protein <em>docking</em> antara kompleks senyawa Fe-ftalosianina (Fe-Pc) dan protein HasAp terhadap protein HasR memiliki nilai <em>Atomic Contact Energy</em> (ACE) positif, yaitu 556,56 kJ/mol. Perbedaan struktur molekul senyawa ftalosianina terbukti mampu mempengaruhi mekanisme aksi terhadap protein target, sehingga hasil studi ini dapat menjadi acuan dalam mendesain struktur senyawa ftalosianina sebagai kandidat photosensitizer dalam terapi fotodinamika.</p><p><span id="docs-internal-guid-a4f8fd6d-7fff-5f66-2ef0-68b87893ec76"><strong><strong>Identification of the Molecular Mechanism of Phthalocyanine Compounds as Photosensitizer Candidates in Photodynamic Therapy by <em>In Silico</em>. </strong></strong>Pathogenic bacteria including <em>Pseudomonas aeruginosa</em> need iron elements to be able to maintain their survival. HasAp is a protein produced by pathogenic bacteria as a source of iron. The HasAp protein will then bind to the outer membrane protein, namely HasR, to be able to forward signals in bacterial cells. Absorption of iron in these pathogenic bacteria can be a strategy for developing therapeutic methods in controlling and preventing infectious diseases caused by pathogenic bacteria <em>Pseudomonas aeruginosa</em>, one of which is by using phthalocyanine as a photosensitizer in photodynamic therapy. This study aims to identify, evaluate, and explore the mechanism of action of phthalocyanine compounds against HasAp proteins, and their effects on the active site of HasR through in silico studies. Ligand-protein docking studies were performed using MGLTools 1.5.6 with AutoDock 4.2 to observe the affinity and molecular interactions between molecules of Fe-phthalocyanine (Fe-Pc) and Ga-phthalocyanine (Ga-Pc) against HasAp protein macromolecules. Furthermore, a protein-protein docking study of the ligand-protein complexes system was simulated to observe its effect on the binding area of the HasR protein macromolecules using PatchDock. Based on the ligand-protein docking results, Fe-phthalocyanine (Fe-Pc) compounds have the best affinity for both HasAp proteins, with a binding energy value of -68.45 kJ/mol and -69.16 kJ/mol, respectively. The protein-protein docking study results between the complex compound Fe-phthalocyanine (Fe-Pc) and HasAp protein against HasR protein have a positive Atomic Contact Energy (ACE) value, with an ACE value of 556.56 kJ/mol. Differences in the molecular structure of phthalocyanine compounds are proven to be able to influence the mechanism of action against the target protein. Therefore, the results of this study can be a reference in designing the structure of phthalocyanine compounds as photosensitizer candidates in photodynamic therapy.</span></p>

Design, Synthesis and In-Vitro Biological Activity of Some New 1,3-Thiazolidine-4-One Derivatives as Chemotherapeutic Agents Using Virtual Screening Strategies

2020 ◽  
Vol 16 ◽  
Author(s):  
Pragya Nayak ◽  
Monica Kachroo
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virtual Screening ◽  
In Silico ◽  
Cancer Cell Line ◽  
Inhibitory Response ◽  
Chemotherapeutic Agents ◽  
Acceptor Site ◽  
Hydrogen Bond Acceptor ◽  
Screening Strategies

: A series of new heteroaryl thiazolidine-4-one derivatives were designed and subjected to in-silico prioritization using various virtual screening strategies. Two series of thiazolidinone derivatives were synthesized and screened for their in-vitro antitubercular, anticancer, antileishmanial and antibacterial (Staphylococcus aureus; Streptococcus pneumonia; Escherichia coli; Pseudomonas aeruginosa) activities. The compounds with electronegative substitutions exhibited positive antitubercular activity, the derivatives possessing a methyl substitution exhibited good inhibitory response against breast cancer cell line MCF-7 while the compounds possessing a hydrogen bond acceptor site like hydroxyl and methoxy substitution in their structures exhibited good in-vitro antileishmanial activity. Some compounds exhibited potent activity against gram positive bacteria Pseudomonas aeruginosa as compared to the standards. Altogether, the designed compounds exhibited good in-vitro anti-infective potential which was in good agreement with the in-silico predictions and they can be developed as important lead molecules for anti-infective and chemotherapeutic drug research.

Insights into the interaction of key biofilm proteins in Pseudomonas aeruginosa PAO1 with TiO2 nanoparticle: An in silico analysis

2019 ◽  
Vol 462 ◽  
pp. 12-25
Author(s):  
Rani Anupama ◽  
Sajitha Lulu ◽  
Rout Madhusmita ◽  
Sundararajan Vino ◽  
Amitava Mukherjee ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
In Silico ◽  
In Silico Analysis ◽  
Tio2 Nanoparticle ◽  
Pseudomonas Aeruginosa Pao1 ◽  
Silico Analysis

The effect of in silico targeting Pseudomonas aeruginosa patatin-like protein D, for immunogenic administration

2018 ◽  
Vol 74 ◽  
pp. 12-19 ◽  
Author(s):  
Alireza Salimi Chirani ◽  
Robabeh Majidzadeh ◽  
Ramin Pouriran ◽  
Mohsen Heidary ◽  
Mohammad Javad Nasiri ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
In Silico

scholarly journals Bruguiera gymnorhiza (L.) Lam. at the Forefront of Pharma to Confront Zika Virus and Microbial Infections—An In Vitro and In Silico Perspective

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5768
Author(s):  
Nabeelah Bibi Sadeer ◽  
Juliano G. Haddad ◽  
Mohammed Oday Ezzat ◽  
Philippe Desprès ◽  
Hassan H. Abdallah ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Zika Virus ◽  
In Silico ◽  
Pathogenic Bacteria ◽  
Scientific Data ◽  
Zikv Infection ◽  
In Silico Docking ◽  
Recent Emergence ◽  
Microbial Infections ◽  
Bruguiera Gymnorhiza

The recent emergence of Zika virus (ZIKV) in Brazil and the increasing resistance developed by pathogenic bacteria to nearly all existing antibiotics should be taken as a wakeup call for the international authority as this represents a risk for global public health. The lack of antiviral drugs and effective antibiotics on the market triggers the need to search for safe therapeutics from medicinal plants to fight viral and microbial infections. In the present study, we investigated whether a mangrove plant, Bruguiera gymnorhiza (L.) Lam. (B. gymnorhiza) collected in Mauritius, possesses antimicrobial and antibiotic potentiating abilities and exerts anti-ZIKV activity at non-cytotoxic doses. Microorganisms Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 70603, methicillin-resistant Staphylococcus aureus ATCC 43300 (MRSA), Salmonella enteritidis ATCC 13076, Sarcina lutea ATCC 9341, Proteus mirabilis ATCC 25933, Bacillus cereus ATCC 11778 and Candida albicans ATCC 26555 were used to evaluate the antimicrobial properties. Ciprofloxacin, chloramphenicol and streptomycin antibiotics were used for assessing antibiotic potentiating activity. ZIKVMC-MR766NIID (ZIKVGFP) was used for assessing anti-ZIKV activity. In silico docking (Autodock 4) and ADME (SwissADME) analyses were performed on collected data. Antimicrobial results revealed that Bruguiera twig ethyl acetate (BTE) was the most potent extract inhibiting the growth of all nine microbes tested, with minimum inhibitory concentrations ranging from 0.19–0.39 mg/mL. BTE showed partial synergy effects against MRSA and Pseudomonas aeruginosa when applied in combination with streptomycin and ciprofloxacin, respectively. By using a recombinant ZIKV-expressing reporter GFP protein, we identified both Bruguiera root aqueous and Bruguiera fruit aqueous extracts as potent inhibitors of ZIKV infection in human epithelial A549 cells. The mechanisms by which such extracts prevented ZIKV infection are linked to the inability of the virus to bind to the host cell surface. In silico docking showed that ZIKV E protein, which is involved in cell receptor binding, could be a target for cryptochlorogenic acid, a chemical compound identified in B. gymnorhiza. From ADME results, cryptochlorogenic acid is predicted to be not orally bioavailable because it is too polar. Scientific data collected in this present work can open a new avenue for the development of potential inhibitors from B. gymnorhiza to fight ZIKV and microbial infections in the future.

scholarly journals Pseudomonas aeruginosa reverse diauxie is an optimized, resource utilization strategy

2020 ◽  
Author(s):  
S. Lee McGill ◽  
Yeni Yung ◽  
Kristopher A. Hunt ◽  
Michael A. Henson ◽  
Luke Hanley ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Systems Biology ◽  
In Silico ◽  
Carbon Sources ◽  
Opportunistic Pathogen ◽  
Metabolic Model ◽  
Wide Distribution ◽  
Overflow Metabolism ◽  
A Genome

AbstractPseudomonas aeruginosa is a globally-distributed bacterium often found in medical infections. The opportunistic pathogen uses a different, carbon catabolite repression (CCR) strategy than many, model microorganisms. It does not utilize a classic diauxie phenotype, nor does it follow common systems biology assumptions including preferential consumption of glucose with an ‘overflow’ metabolism. Despite these contradictions, P. aeruginosa is competitive in many, disparate environments underscoring knowledge gaps in microbial ecology and systems biology. Physiological, omics, and in silico analyses were used to quantify the P. aeruginosa CCR strategy known as ‘reverse diauxie’. An ecological basis of reverse diauxie was identified using a genome-scale, metabolic model interrogated with in vitro omics data. Reverse diauxie preference for lower energy, nonfermentable carbon sources, such as acetate or succinate over glucose, was predicted using a multidimensional strategy which minimized resource investment into central metabolism while completely oxidizing substrates. Application of a common, in silico optimization criterion, which maximizes growth rate, did not predict the reverse diauxie phenotypes. This study quantifies P. aeruginosa metabolic strategies foundational to its wide distribution and virulence.

scholarly journals Berberine Derivatives as Pseudomonas aeruginosa MexXY-OprM Inhibitors: Activity and In Silico Insights

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6644
Author(s):  
Giorgia Giorgini ◽  
Gianmarco Mangiaterra ◽  
Nicholas Cedraro ◽  
Emiliano Laudadio ◽  
Giulia Sabbatini ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
In Silico ◽  
Rational Design ◽  
Specific Binding ◽  
In Silico Analysis ◽  
In Vitro Assays ◽  
Binding Modes ◽  
Starting Point ◽  
Berberine Derivatives

The natural alkaloid berberine has been demonstrated to inhibit the Pseudomonas aeruginosa multidrug efflux system MexXY-OprM, which is responsible for tobramycin extrusion by binding the inner membrane transporter MexY. To find a structure with improved inhibitory activity, we compared by molecular dynamics investigations the binding affinity of berberine and three aromatic substituents towards the three polymorphic sequences of MexY found in P. aeruginosa (PAO1, PA7, and PA14). The synergy of the combinations of berberine or berberine derivatives/tobramycin against the same strains was then evaluated by checkerboard and time-kill assays. The in silico analysis evidenced different binding modes depending on both the structure of the berberine derivative and the specific MexY polymorphism. In vitro assays showed an evident MIC reduction (32-fold and 16-fold, respectively) and a 2–3 log greater killing effect after 2 h of exposure to the combinations of 13-(2-methylbenzyl)- and 13-(4-methylbenzyl)-berberine with tobramycin against the tobramycin-resistant strain PA7, a milder synergy (a 4-fold MIC reduction) against PAO1 and PA14, and no synergy against the ΔmexXY strain K1525, confirming the MexY-specific binding and the computational results. These berberine derivatives could thus be considered new hit compounds to select more effective berberine substitutions and their common path of interaction with MexY as the starting point for the rational design of novel MexXY-OprM inhibitors.

scholarly journals Analisa In Silico Kunyit (Curcuma longa) sebagai Inhibitor Murine Double Minute 2 Protein untuk Terapi Glioblastoma Multiforme

2020 ◽  
Vol 3 (2) ◽  
pp. 82
Author(s):  
Benny Iswanto Pantoro ◽  
Nancy Margarita Rehatta ◽  
Siti Khaerunnisa ◽  
Anna Surgean Veterini ◽  
Yuani Setiawati
Keyword(s):  
Glioblastoma Multiforme ◽  
Binding Energy ◽  
In Silico ◽  
Curcuma Longa ◽  
Double Minute ◽  
Murine Double Minute ◽  
Autodock 4.2 ◽  
Tumor Suppresor Gene

<p>Tumor otak meliputi berbagai kanker yang tumbuh dari sel otak (tumor otak primer) ataupun berasal dari tumor sistemik yang mengalami metastasis ke otak (tumor otak sekunder). Dari seluruh tipe tumor otak primer, Glioblastoma Multiforme merupakan tumor otak yang paling sering dijumpai dan merupakan salah satu yang paling ganas. Pada 85% kasus Glioblastoma Multiforme, umumnya ditemukan kaitan dengan adanya gangguan tingkat molekuler pada jalur tumor suppresor gene p53, sehingga semakin banyak terapi yang dikembangkan dengan berfokus pada jalur ini. Salah satu jalur yang dapat dipakai sebagai model terapi adalah menginhibisi protein murine double minute 2 yang merupakan inhibitor dari p53. Kunyit (<em>curcuma longa</em>) adalah salah satu tanaman tradisional yang sudah sangat sering digunakan dalam dunia medis dan berbagai ekstrak nya telah diteliti mempunyai efek anti-kanker.</p>Penelitian ini adalah sebuah studi <em>in silico</em> yang meneliti potensi berbagai bahan kimia aktif dari kunyit sebagai inhibitor pada protein murine double minute 2 menggunakan AutoDock 4.2 dan berdasarkan prinsip algoritma genetik Lamarckian. Hasil docking menunjukkan <em>binding energy</em> berkisar dari rentang -4.81 kcal/mol sampai -2.34 kcal/mol, dengan senyawa curcumenol mempunyai <em>binding energy</em> yang paling kecil dan curcumin mempunyai <em>binding energy </em>yang paling besar. Studi ini dapat digunakan sebagai dasar untuk melakukan penelitian lebih lanjut (<em>in vivo</em> dan <em>in vitro</em>) terkait bahan kimia aktif kunyit dan efek nya sebagai terapi Glioblastoma Multiforme.

Sign in / Sign up

Export Citation Format

Share Document