Judul: Cephalosporins, in silico, molecular docking, molecular dynamics, mutations
Abstrak: Sefalosporin merupakan antibiotik β-laktam semisintetik yang dapat digunakan untuk mengatasi penyakit infeksi yang disebabkan oleh bakteri grampositif dan gram-negatif. Semisintetik sefalosporin disintesis dari 7-aminocephalosporanic acid (7-ACA), yang didapatkan dari pemutusan gugus asil secara kimiawi atau reaksi enzimatis dari sefalosporin C (CPC). Konversi CPC menggunakan reaksi enzimatis satu langkah membutuhkan sefalosporin C asilase (CPC asilase), tetapi CPC asilase alami memiliki aktifitas yang rendah terhadap substrat CPC. Rekayasa secara pendekatan in silico digunakan untuk mendapatkan mutan CPC asilase dari Pseudomonas sp. Strain SE83 yang memiliki potensi untuk meningkatkan aktivitas berdasarkan energi bebas ikatan dan stabilitasnya. Penambatan molekul oleh oleh Autodock Vina menggunakan energi bebas ikatan, ikatan hidrogen, dan kontak hidrofobik menunjukkan mutan V25βR, F55βR, L154βY, dan I176βH memiliki stabilitas yang lebih baik. Simulasi dinamika molekul oleh AMBER18 menunjukkan mutan I176βH memiliki potensi terbaik dengan energi ikat rata-rata sebesar -54,71 kkal mol-1, dan stabilitas yang baik berdasarkan RMSD, RMSF, dan okupansi ikatan hidrogen selama 50 ns., Chephalosporins are the semisynthetic β-lactam antibiotics for the treatment of infection diseases caused by gram-positive and gram-negative bacteria. Semisynthetic cephalosporins are synthesized from 7-aminocephalosporanic acid (7-ACA), which is produced by chemical deacylation or enzymatic conversion of cephalosporin C (CPC). The single-step enzymatic conversion of CPC uses cephalosporanic C acylase (CPC acylase), however known natural CPC acylase has a very low activity on the substrat CPC. In Silico engineering approach was used to discover a mutant of CPC acylase from Pseudomonas sp. Strain SE83 that had potential to increase the activity based on its free energy binding and stability. Molecular docking by Autodock Vina using binding free energy, hydrogen bonds, and hydrophobic interaction shown that mutants of V25βR, F55βR, L154βY, and I176βH had a better stability. Molecular dynamics simulations by AMBER18 shown that I176βH mutant has the best potential with an average binding free energy value of -54,71 kcal mol-1, and good stability based on the RMSD, RMSF, and hydrogen bond occupancy in the period of 50 ns.
Keyword: In Silico, Sefalosporin, Dinamika Molekul

Judul: Studi In Silico Potensi Senyawa Fenolik sebagai Inhibitor Protein Resistensi Antibiotik pada Salmonella
Abstrak: Kontaminasi Salmonella spp. pada daging ayam telah menyebabkan kasus penyakit bawaan pangan yang dapat berujung pada kematian bila tidak segera ditangani. Resistensi antibiotik menjadi permasalahan utama dalam mengendalikan infeksi patogen. Penggunaan senyawa non-antibiotik (adjuvan) untuk menghambat mekanisme resistensi antibiotik mulai banyak dikaji sebagai upaya yang efektif dalam mengatasi infeksi multidrug-resistant (MDR) Salmonella. Senyawa fenolik dalam pangan nabati terbukti memiliki aktivitas antimikroba dan dapat menjadi alternatif adjuvan untuk menghambat mekanisme resistensi pada Salmonella spp. Penelitian ini bertujuan menentukan senyawa fenolik yang berpotensi sebagai inhibitor protein resistensi antibiotik pada Salmonella melalui studi in silico. Penelitian dilaksanakan melalui empat tahapan, yakni prediksi dan evaluasi model struktur 3D protein; pencarian dan skrining ligan uji; simulasi penambatan (docking) molekuler; serta simulasi dinamika molekul dan ensemble docking. Struktur 3D protein diprediksi dengan SWISS-MODEL (pemodelan homologi), I-TASSER (pemodelan threading), dan AlphaFold2 (pemodelan ab initio). Simulasi penambatan (docking) molekuler dilakukan dengan AutoDock Vina menggunakan konformasi tunggal (rigid) dan konformasi fleksibel (ensemble) dari protein target. Protein target yang digunakan dalam penelitian ini adalah β-laktamase kelas A TEM-1 dan aminoglikosida nukleotidiltransferase AadA. TEM-1 menyebabkan resistensi β-laktam melalui hidrolisis ikatan amida pada antibiotik, sementara AadA menyebabkan resistensi aminoglikosida melalui transfer gugus adenil ke antibiotik. Pemodelan homologi menghasilkan model dengan kualitas yang paling baik dalam prediksi struktur 3D TEM-1 dan AadA berdasarkan plot Ramachandran, G-factors, dan ERRAT. Di sisi lain, dua puluh senyawa fenolik sebagai ligan uji diprediksi dapat diserap dengan baik secara oral, menunjukkan bioavailabilitas yang baik, dan tidak berpotensi menimbulkan bahaya bagi tubuh. Penggunaan konformasi ensemble protein menghasilkan mode pengikatan yang relatif lebih baik daripada penggunaan konformasi tunggal. Kompleks TEM-1 dengan ampisilin dan ligan uji membentuk interaksi dengan empat residu pada situs katalitik (Ser68, Lys71, Ser128, dan Glu164), Tyr103, Asn130, dan Asn168. Kompleks AadA dengan gentamisin dan ligan uji membentuk interaksi dengan Trp112, Asp182, His185, dan residu katalitik Glu87. Asam elagat, kuersetin, dan mirisetin berpotensi sebagai inhibitor TEM-1 dan AadA. Sianidin juga berpotensi sebagai inhibitor TEM-1 dan kaempferol berpotensi sebagai inhibitor AadA. Gugus hidroksil yang terikat pada cincin fenil dan cincin heterosiklik memiliki peran penting sebagai donor ikatan hidrogen dalam interaksinya dengan situs pengikatan protein target. Penelitian lebih lanjut perlu dilakukan untuk memvalidasi hasil analisis penambatan molekuler dan membuktikan aktivitas penghambatan senyawa fenolik terhadap protein target.
Keyword: adjuvant, antibiotic resistance, molecular docking, phenolic compound, Salmonella

Judul: Characteristic of Overshooting Top (OT) Based on  Himawari  8  Satellite  as  a  Convective  Cloud  Feature  that  Generates  Extreme Weather in the Java Island Region
Abstrak: Overshooting Top (OT) is a feature at the top of a convective cloud that is associated with extreme weather. Research on OT in tropical Indonesia is still very limited. The existence of geostationary satellites with wide area coverage and fast frequency observations is useful for observing the fast dynamics of the OT life cycle. Therefore, this study intends to analyze the relationship between OT and extreme weather, updraft and thermodynamic conditions of OT when extreme weather occurs, the best objective method for detecting OT in the day time and night time, and the spatiotemporal distribution of OT in the tropical region of Java Island during the 2018-2021 period. Based on visual analysis using visible channel and Himawari 8 sandwich products, 87% of extreme weather events in Java were accompanied by the appearance of OT. It indicates that the presence of the OT pattern is a convection cloud pattern or feature that is closely related to extreme weather events for the Java Island region. The existence of a time lag between the appearance of OT and extreme weather events on Java Island indicates that the OT of convection cloud can be used as a precursor or nowcasting for the appearance of extreme weather. Most of the convective cloud OT features during extreme weather events on Java Island have altitude that were only able to exceed the altitude of the equilibrium level and few were able to exceed the tropopause level of 9 km – 16 km. The difference in atmospheric conditions during extreme weather events on Java Island, which is in the tropics and subtropics, is a strong and unstable convective energy condition characterized by a larger CAPE, as well as unstable KI, LI, SI and TTI values. It is offset by kinematic factors in the form of a weak vertical wind shear (bulk wind shear 0-6 km) and a higher freezing point height. The difference between extreme weather events in the Java Island region and other tropical regions compared to subtropical regions is the strong updraft speed of convection clouds. The IRW Texture COMB algorithm based on the IRW-Texture Gradient modification and the COMB algorithm shows a significant increase in quality for detecting OT and non-OT pixels in Java. Rainy days with rainfall > 50 mm/day are very common in areas with an altitude of > 500 m. On the other hand, the level of convection activity which is indicated by the presence of OT and lightning is significantly reduced in this area. OT of convective clouds appear more frequently during the DJF season and less frequently during the JJA season. OT often appears during the day time and rarely at night time. Most OTs appear in the central part, away from the south and north coasts of Java Island during the day, while OTs that appear near the south and north coasts of Java Island can appear in the morning or afternoon.
Keyword: convective clouds, extreme weather, Overshooting Tops, Himawari 8 Satellite