Hasil Pencarian  ::  Simpan CSV :: Kembali

"With chapters provided by international leading experts, this book covers the recent advances in protein and peptide mass spectrometry. Focusing on the pharmaceutical industry, it addresses both emerging techniques, including imaging mass spectrometry, ion mobility, and microwave-assisted mass spectrometry, and recent applications, including pharmaceutical analysis throughout the drug development cycle. The book stresses practice and applications, providing real world examples from industry contributors. After overviewing methodology and discussing recent studies, the remaining chapters address newer techniques for determining protein structure, interactions with peptides, proteins, and ligands, and protein folding and unfolding."

"Focused manuscript on the potential use/role of miRNAs in bioprocessing, specifically the production of complex proteins in mammalian cells. With that in mind I propose a draft list of topics/chapters along the following lines, intro on CHO/bioprocessing/engineering challenges to set scene, genomic organization, biogenesis and mode of action, Identifying miRNA targets, computational prediction, transcriptomics, proteomices, UTR analysis, etc., miRNA expression in Chinese hamster ovary cells, miRNAs as engineering targets: pathway manipulation to impact bioprocess phenotypes, miRNAs as biomarkers, detection methods : northern, PCR, hybridization arrays, next gen seq, manipulation of expression in cultured cells : transient/stable disregulation, knockout."

"Penyakit demam berdarah (dengue) merupakan masalah kesehatan yang serius dan hingga saat ini belum ada langkah spesifik untuk mengobati penyakit ini. Dengue merupakan penyakit yang disebabkan oleh virus dengue (DENV), suatu flavivirus yang terselubung oleh envelope. Infeksi DENV dimulai dengan inisiasi proses fusi antara envelope virus dengan membran sel host, transfer materi genetik ke dalam sel target yang diikuti dengan replikasi serta pembentukan virus baru. Proses fusi ini dimediasi oleh peptida fusi yang diperkirakan merupakan suatu segmen antara residu D98-G112 pada protein envelope (E) DENV. Penelitian terdahulu menunjukkan bahwa peptida fusi ini tersembunyi di dalam suatu cavity dan akan diposisikan pada ujung domain II protein E DENV akibat perubahan konformasi sewaktu proses fusi terjadi. Penelitian ini bertujuan untuk merancang peptida siklis disulfida yang dapat menempati cavity ini dan berinteraksi dengan peptida fusi, sehingga mengganggu perubahan konformasi yang terjadi dan menginhibisi proses fusi. Pendekatan komputasi dilakukan untuk memprediksi afinitas dan stabilitas antara ligan peptida siklis disulfida dengan protein E DENV. Simulasi molecular docking dan molecular dynamics dilakukan dengan software MOE 2008.10. Screening terhadap 1320 ligan menghasilkan 3 ligan terbaik, CLREC, CYREC dan CFREC yang dapat berinteraksi dengan cavity target dan juga segmen peptida fusi. Ketiga ligan ini menunjukkan afinitas yang baik dengan target berdasarkan nilai energi bebas ikatan dan interaksi protein-ligan yang terbentuk. Stabilitas kompleks protein-ligan dianalisis dengan metode molecular dynamics. Hasil simulasi molecular dynamics menunjukkan bahwa hanya CLREC yang menunjukkan kestabilan konformasi protein-ligan dan mempertahankan interaksi antara ligan dengan cavity target. Oleh karena itu CLREC memiliki potensi sebagai inhibitor fusi DENV.

---

Dengue has been a major health concern and currently there is no available option to treat the infection. It is an arboviral disease caused by dengue virus (DENV), an enveloped flavivirus. DENV initiates fusion process between viral envelope and host cell membrane, transfers its viral genome into target cell and infects host. This fusion process is mediated by a fusion peptide which was predicted to be a segment of DENV envelope (E) glycoprotein located between residues D98 ? G112. Recent studies showed that this segment is hidden inside a cavity and will undergo conformational changes to be positioned at the tip of domain II E glycoprotein when fusion occurs. Our research is focused on designing disulfide cyclic peptides that can fit into this cavity and interact with fusion peptide, interrupt conformational changes and therefore inhibit the fusion process.

Computational approaches were conducted to calculate the binding affinity and stability of disulfide cyclic peptide ligands with target DENV E glycoprotein. Molecular docking and molecular dynamics simulation were performed using Molecular Operating Environment 2008.10 software (MOE 2008.10). Screening of 1320 designed ligands resulted in 3 best ligands, CLREC, CYREC and CYREC that can form interaction with target cavity and peptide fusion. These ligands showed good affinity with target DENV E glycoprotein based on free binding energy and interactions. To evaluate protein-ligand stability, we performed molecular dynamic simulation. Only CLREC showed protein-ligand stability and maintained interaction between ligand and target cavity. Therefore we propose CLREC as potential DENV fusion inhibitor candidate"