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"Inflamasi merupakan respon fisiologis terhadap cedera jaringan dan infeksi. Inflamasi dapat ditangani dengan sejumlah obat seperti obat anti-inflamasi nonsteroida inhibitor selektif COX-2. Benzimidazol merupakan senyawa penuntun yang memiliki berbagai aktivitas farmakologis, salah satunya sebagai anti-inflamasi. Penelitian ini dilakukan secara in silico dengan metode penambatan molekuler senyawa turunan benzimidazol Mannich terhadap COX-1 dan COX-2 untuk mengetahui potensi anti-inflamasi senyawa menggunakan Autodock 4 dan Autodock Vina. Hasil validasi menunjukkan bahwa nilai RMSD Autodock 4 dan Autodock Vina dibawah 2 Å sehingga penambatan molekuler dilakukan pada kedua perangkat lunak. Pada penambatan molekuler menggunakan Autodock 4, turunan benzimidazol substituen vanilin 2,6-dimetilmorfolin diprediksi paling selektif terhadap COX-2 yaitu rasio Ki COX-1/2 senilai 162,79. Pada penambatan molekuler menggunakan Autodock Vina, turunan benzimidazol substituen vanilin dietilamina diprediksi paling selektif terhadap COX-2 yaitu rasio Ki COX-1/2 senilai 112,88. Visualisasi interaksi pada Autodock 4 dan Autodock Vina juga menunjukkan hasil yang sedikit berbeda. Dengan demikian terdapat dua buah kesimpulan yang diperoleh: senyawa turunan benzimidazol Mannich memiliki potensi anti-inflamasi inhibitor selektif COX-2, dan terdapat perbedaan interaksi yang muncul di antara penambatan molekuler terhadap Autodock 4 dan Autodock Vina.

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Inflammation is a physiological response occurred by tissue injury and infection. Inflammation can be treated with drugs such as COX-2 selective NSAID. Benzimidazole is a leading compound that has many pharmacological activities such as anti-inflammation. In this study, in silico testing is carried out with molecular docking into Mannich benzimidazole derivatives against COX-1 and COX-2 using Autodock 4 and Autodock Vina to determine the anti-inflammatory potential of the test compounds. Validation result shows that both the RMSD value of both Autodock 4 and Autodock Vina are below 2 Å. Hence, molecular docking is conducted with both programs. Autodock 4 result shows that benzimidazole derivative with vanillin 2,6-dimethylmorpholine substitution is predicted to be the most selective against COX-2 with the Ki COX-1/2 ratio of 162.79. Autodock Vina result shows that benzimidazole derivative with vanillin diethylamine substitution is predicted to be the most selective against COX-2 with the Ki COX1/2 ratio of 112.88. Interaction visualization of Autodock 4 and Autodock Vina also shows few differences, yielding two conclusions from the study: Mannich benzimidazole derivatives have anti-inflammatory potential selective to COX-2 and there are few differences appeared in molecular docking with Autodock 4 and Autodock Vina."

"Diabetes melitus (DM) merupakan penyakit kronis serius yang terjadi karena adanya gangguan sekresi dan resistensi insulin. Inhibitor dipeptidil peptidase-4 (DPP-4) merupakan salah satu golongan senyawa antidiabetes yang minim efek samping dibandingkan golongan obat diabetes lainnya. Mekanisme kerja inhibitor DPP-4 adalah memperpanjang dan meningkatkan aktivitas Glucagon Like Peptide-1 (GLP-1). Namun, beberapa inhibitor DPP-4 memiliki efek samping yang tidak diinginkan seperti nyeri sendi dan radang pankreas. Efek samping tersebut diindikasikan berkaitan dengan penghambatan terhadap dipeptidil peptidase-8 (DPP-8) dan dipeptidil peptidase-9 (DPP-9). Kurkumin merupakan senyawa bioaktif yang memiliki berbagai aktivitas seperti antidiabetes, antikanker, dan antihipertensi. Namun, efikasi klinik kurkumin sangat terbatas karena bioavailabilitasnya yang rendah. Pendekatan hibridisasi kurkumin dengan fragmen farmakofor vildagliptin diharapkan dapat memperbaiki keterbatasan kurkumin. Pada penelitian tahap awal ini, dilakukan pengujian in silico yaitu penambatan molekuler senyawa hibrida dari vildagliptin dan analog kurkumin terhadap DPP-4, DPP-8, dan DPP-9 menggunakan program AutoDock dan AutoDock Vina yang divalidasi menggunakan nilai Root Mean Square Deviation (RMSD) Redocking. Hasil penambatan molekuler senyawa hibrida dari vildagliptin dan analog kurkumin terhadap DPP-4, DPP-8, dan DPP-9 menggunakan 10 senyawa didapatkan tiga senyawa yang lebih selektif terhadap DPP-4 yaitu senyawa dengan substituen hidroksil dan metoksi, substituen metil, dan substituen trifluorometil masing-masing memiliki nilai selektivitas sebesar 0,254, 0,8, 0,214 . Nilai energi ikatan bebas ketiga senyawa tersebut masing-masing sebesar -9,42 kkal/mol, -8,95 kkal/mol, dan -8,41 kkal/mol. Dapat disimpulkan bahwa senyawa hibrida dari vildagliptin dan analog kurkumin memiliki potensi sebagai penghambat DPP-4, tetapi hanya terdapat tiga senyawa yang lebih selektif terhadap DPP-4.

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Diabetes mellitus (DM) is a chronic disease that occurs due to impaired secretion and insulin resistance. Dipeptidyl peptidase-4 (DPP-4) inhibitors are one class of antidiabetic compounds having minimal side effects compared to other classes of antidiabetic drugs. The mechanism of action of DPP-4 inhibitors is to extend and increase the activity of Glucagon Like Peptide-1 (GLP-1). However, some of the DPP-4 inhibitors have side effects such as joint pain and pancreatitis. These side effects are thought to have an association with inhibition of dipeptidyl peptidase-8 (DPP-8) and dipeptidyl peptidase-9 (DPP-9). Curcumin is a bioactive compound that has various activities such as antidiabetic, anticancer, and antihypertensive. However, the clinical efficacy of curcumin is very limited due to its poor bioavailability. Curcumin hybridization approach with vildagliptin pharmacophore fragments is expected to improve the limitations of curcumin. In this preliminary study, in silico testing was carried out by molecular docking of the hybrid compound of vildagliptin and curcumin analogue against DPP-4, DPP-8, and DPP-9 using the AutoDock and AutoDock Vina programs which were validated using the Redocking Root Mean Square Deviation (RMSD) values. The results of molecular docking of the 10 hybrid compounds of vildagliptin and curcumin analogue to DPP-4, DPP-8, and DPP-9 show that three compounds are more selective towards DPP-4. These namely compounds with hydroxyl and methoxy, methyl, and trifluoromethyl substituents, which have selectivity value of 0.254, 0.8, 0.214, respectively. The free binding energy of the three compounds is -9.42 kcal/mol, -8.95 kcal/mol, and -8.41 kcal/mol. It can be concluded that the hybrid compound of vildagliptin and curcumin analogue has the potential to inhibit DPP-4, but there are only three compounds that are more selective towards DPP-4."

"Inflamasi adalah respon dari sistem imun tubuh terhadap hal yang dapat membahayakan tubuh, seperti patogen, sel yang rusak, zat beracun, atau radiasi. Proses inflamasi yang berlebihan dapat menimbulkan beberapa penyakit kronis, seperti inflammatory bowel disease, diabetes melitus tipe I, artritis, dan kanker. Beberapa terapi inflamasi menargetkan untuk menghambat metabolisme asam arakidonat jalur siklooksigenase (COX-1 dan COX-2) dan 5-lipoksigenase (5-LOX). Kurkumin merupakan senyawa alami yang memiliki beberapa aktivitas antiinflamasi dan antiproliferasi. Namun, kurkumin memiliki kestabilan dan kelarutan yang buruk. Untuk memperbaiki kekurangan tersebut beberapa modifikasi struktur telah dilakukan, antara lain siklisasi gugus 1,3-dikarbonil membentuk cincin pirazol dan substitusi gugus basa Mannich. Pada penelitian ini dilakukan pengujian in silico dengan penambatan molekuler senyawa turunan kurkumin pirazol Mannich terhadap COX-1, COX-2, dan 5-LOX untuk memprediksi potensi aktivitas antiinflamasi senyawa tersebut. Proses validasi dilakukan dengan program AutoDock dan AutoDock Vina. Hasil validasi menunjukkan bahwa program AutoDock mempunyai nilai Root Mean Square Deviation (RMSD) yang lebih baik dibandingkan dengan AutoDock Vina. Hasil penambatan molekuler menunjukan bahwa seluruh senyawa turunan kurkumin pirazol Mannich memiliki selektivitas terhadap COX-2 dibandingkan terhadap COX-1. Senyawa yang memiliki energi bebas ikatan terendah berturut-turut pada COX-1, COX-2, dan 5-LOX adalah kurkumin pirazol tersubstitusi basa Mannich metilpiperazin  (-7,47 kkal/mol), dimetilmorfolin (-11,01 kkal/mol), dan morfolin (-6,55 kkal/mol). Senyawa yang memiliki nilai selektivitas tertinggi adalah kurkumin pirazol tersubstitusi basa Mannich dibutilamin dan morfolin dengan nilai S 0,0001. Maka dari itu, dapat disimpulkan bahwa senyawa kurkumin pirazol Mannich diprediksi memiliki potensi anti-inflamasi melalui penghambatan COX-2 selektif.

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Inflammation is the response of the body's immune system to things that can harm the body, such as pathogens, damaged cells, toxic substances, or radiation. Excessive inflammatory processes can cause several chronic diseases, such as inflammatory bowel disease, type I diabetes mellitus, arthritis, and cancer. Some inflammatory therapies target to inhibit the arachidonic acid metabolism of the cyclooxygenase pathway (COX-1 and COX-2) and 5-lipoxygenase (5-LOX). Curcumin is a natural compound having several biological activities such as anti-inflammatory and antiproliferation. However, curcumin has poor stability and solubility. To improve these deficiencies several structural modifications have been done, such as cyclization of the 1,3-dicarbonyl moiety to form pyrazole ring and the substitution of Mannich base group. In this study, an in silico test was carried out by molecular docking of curcumin pyrazole Mannich derivatives against COX-1, COX-2, and 5-LOX to predict the anti-inflammatory activity potential of the compounds. The validation process was performed using the AutoDock and AutoDock Vina programs. The validation results indicated that the AutoDock program showed a better value of Root Mean Square Deviation (RMSD) compared to AutoDock Vina. The results of the molecular docking study showed that all pyrazole curcumin Mannich derivatives have selectivity to COX-2 compared to COX-1. Compounds having the lowest free binding energy against COX-1, COX-2, and 5-LOX respectively were curcumin pyrazole substituted Mannich base of methylpiperazine (-7.47 kcal/mol), dimethylmorpholine (-11.01 kcal/mol), and morpholine (-6.55 kcal/mol). The compounds having the highest selectivity value are curcumin pyrazole substituted Mannich base of dibutylamine and morpholine with a value of S 0.0001. Therefore, it can be concluded that curcumin pyrazole Mannich derivatives were predicted to have anti-inflammatory potential by selective inhibitory to COX-2.

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"Malaria menjadi masalah kesehatan global utama karena banyaknya kejadian resistensi obat, sedangkan ketersediaan obat yang efektif juga terbatas, sehingga mendasari pentingnya pengembangan obat antimalaria yang baru. Berbagai penelitian perancangan obat yang mentarget berbagai enzim terus dilakukan, terutama enzim Plasmodium falciparum Enoyl Acyl Carrier Protein Reductase (PfENR). Penapisan virtual sebagai salah satu metode pendekatan in silico telah digunakan pada pencarian senyawa penuntun dari basis data senyawa ataupun dari basis data bahan alam sebagai inhibitor PfENR. Pada penelitian ini dilakukan penapisan virtual basis data senyawa tanaman obat di Indonesia pada PfENR. Penapisan dilakukan dengan menggunakan piranti lunak AutoDock dan AutoDock Vina. Pada AutoDock Vina dilakukan validasi terlebih dahulu sedangkan pada AutoDock tidak dilakukan karena telah divalidasi oleh peneliti sebelumnya. Hasil validasi AutoDock Vina diperoleh grid box terbaik yaitu 80x80x80. Berdasarkan hasil penapisan diperoleh 10 peringkat senyawa terbaik dari tiap metode dan 5 senyawa irisan dari kedua metode yaitu jacoumaric acid, beta sitosterol glucoside (lyoniside), limacine, leucadenone B, dan yuehchukene.

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Malaria is a major global public health problem. The alarming spread of its drug resistance and limited number of effective drugs available underline how important it is to discover new antimalarial drug. Various researches have been done to design drug targeting Plasmodium falciparum Enoyl Acyl Carrier Protein Reductase (PfENR) enzymes. Virtual screening as in silico approach has been used to find lead molecules from compound library or natural database as PfENR inhibitors. In this research, virtual screening of Indonesian herbal database was done to PfENR. Virtual screening was done using AutoDock and AutoDock Vina. AutoDock Vina was validated beforehand in order to obtain the best grid box while the virtual screening using AutoDock is not validated because it has been validated by previous researchers. Based on this research, the best grid box for AutoDock Vina is 80x80x80. Top ten ranked compounds were obtained for each method and five the same compound of the two methods that was jacoumaric acid, beta sitosterol glucoside (lyoniside), limacine, leucadenone B, and yuehchukene."

"The present book presents a collection of simulation studies of this behaviour. Employing conceptually simple but comprehensive models, the fundamental material properties of shape memory alloys are qualitatively explained from first principles. Using contemporary methods of molecular dynamics simulation experiments, it is shown how microscale dynamics may produce characteristic macroscopic material properties. The work is rooted in the materials sciences of shape memory alloys and covers thermodynamical, micro-mechanical and crystallographical aspects."

"Virus dengue (DENV) telah menyebar luas di berbagai penjuru dunia, terutama pada daerah beriklim tropis. Pengobatan yang efektif terhadap infeksi DENV belum tersedia walaupun telah dikembangkan beberapa kandidat vaksin. Pengobatan yang dilakukan saat ini hanya untuk mengurangi gejala sakit dan mengurangi risiko kematian. Oleh karena itu, dibutuhkan suatu pengobatan yang bersifat antiviral. Protein envelope merupakan salah satu protein struktural DENV yang diketahui dapat menjadi target inhibitor antiviral dan berperan khusus dalam proses fusi. Penelitian ini bertujuan untuk screening peptida siklis komersial yang digunakan sebagai inhibitor protein envelope DENV melalui molecular docking dan molecular dynamics pada temperatur 310K dan 312K. Screening 301 peptida siklis komersial melalui molecular docking menghasilkan 10 ligan terbaik dan berdasarkan interaksi ikatan hidrogen dan kontak residu pada cavity protein envelope didapatkan tiga ligan terbaik yang dapat memasuki cavity protein envelope secara keseluruhan. Ketiga ligan tersebut diuji melalui ADME-Tox dan didapatkan ligan terbaik, yaitu BNP (7-32), porcine. Hasil simulasi molecular dynamics pada temperatur 310K dan 312K menunjukan bahwa ligan dapat mempertahankan interaksi dengan cavity target, sehingga ligan BNP (7-32), porcine dapat dijadikan kandidat antiviral untuk DENV.

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Dengue virus ( DENV) has spread throughout the world, especially in tropical climates. Effective treatment of DENV infection is not yet available although several candidate vaccines have been developed. Treatment at this time is only to reduce symptoms and reduce the risk of death. Therefore, antiviral treatment is very needed. Envelope Protein is one of the structural proteins of DENV which is known could be a target of antiviral inhibitors and plays a special role in the fusion process.

This research aims to screen the commercial cyclic peptides which are used as inhibitors of envelope protein DENV through molecular docking and molecular dynamics at 310K and 312K. Screening of commercial cyclic peptides through molecular docking ligands obtained best 10 ligands then examined the interaction between hydrogen bonding and residue contacts of the cavity envelope protein and obtained best three ligands which could enter the cavity of envelope protein overall. The three ligands were predicted through the ADME-Tox and obtained the best ligands, namely BNP (7-32), porcine. The results of molecular dynamics simulations at 310K and 312K revealed that ligand can maintain interaction with the cavity of the target."

"The lock-and-key principle formulated by Emil Fischer as early as the end of the 19th century has still not lost any of its significance for the life sciences. The basic aspects of ligand-protein interaction may be summarized under the term 'molecular recognition' and concern the specificity as well as stability of ligand binding. Molecular recognition is thus a central topic in the development of active substances, since stability and specificity determine whether a substance can be used as a drug. Nowadays, computer-aided prediction and intelligent molecular design make a large contribution to the constant search for, e. g., improved enzyme inhibitors, and new concepts such as that of pharmacophores are being developed."

"Protein envelope merupakan salah satu protein struktural virus dengue (DENV) yang berperan dalam proses fusi virus ke dalam sel host. Proses fusi berperan penting dalam mentransfer materi genetik ke dalam sel host untuk pembentukan virus baru. Proses fusi dimediasi oleh perubahan konformasi struktur protein dimer menjadi trimer. Penelitian terdahulu menunjukkan adanya cavity pada struktur dimer protein envelope. Adanya suatu ligan yang dapat menempati cavity pada protein envelope dapat menstabilkan struktur dimer atau menghambat transisi dimer protein envelope menjadi bentuk trimer sehingga proses fusi dapat dicegah. Penelitian ini bertujuan untuk merancang peptida siklis dengan ikatan prolin-prolin yang digunakan sebagai inhibitor fusi protein envelope DENV melalui molecular docking dan simulasi molecular dynamics. Screening 3883 peptida siklis dengan ikatan prolin-prolin melalui molecular docking didapatkan lima ligan terbaik. Sifat farmakologi dan toksisitas dari ligan terbaik diprediksi secara in silico. Hasil prediksi menyatakan bahwa PYRRP merupakan ligan terbaik. Ligan PAWRP juga dipilih sebagai ligan terbaik karena memiliki afinitas yang baik dengan cavity protein. Stabilitas kompleks protein-ligan dianalisa dengan simulasi molecular dynamics. Hasil simulasi molecular dynamics menunjukkan bahwa ligan PYRRP dapat membuat struktur dimer protein envelope DENV stabil pada 310 K dan 312 K. Sedangkan ligan PAWRP lebih aktif membentuk kompleks dengan protein envelope DENV pada 310 K dibandingkan pada 312 K. Oleh karena itu, ligan PYRRP memiliki potensi sebagai inhibitor fusi DENV.

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Envelope protein is one of the structural proteins of DENV engaged in virus fusion process into the host cell. Fusion process plays an important role in transfering genetic material into the host cells to form a new virion. The fusion process is mediated by the conformation change of protein structure from dimer to trimer state. The previous research shows the existing cavity on the dimer structure of the envelope protein. The existing ligand that is able to get into cavity on the envelope protein can stabilize the dimer structure or hamper the transition of dimer protein into trimer, so that the fusion process can be prevented.

This aims of research to design the cyclic peptide by prolin-prolin bond as fusion inhibitor of DENV envelope protein through molecular docking and molecular dynamics simulation. Screening 3883 of cyclic peptide by prolin-prolin bond through molecular docking got the best five ligans as inhibitors. Pharmacological and toxicity properties of the best ligans were predicted by in silico. The result expressed that PYRRP is the best ligand. PAWRP is also chosen as the best ligan because it has a good affinity with cavity protein. Complex stability of ligan protein was analyzed by molecular dynamics simulation.

The result shows that PYRRP ligand can make the dimer structure of DENV envelope protein stable in 310 K and 312 K. While PAWRP ligand actively forms the complexity with the DENV envelope protein in 310 K compared to 312 K. Thus the PYRRP ligand has a potential as DENV fusion inhibitor."