Objectives: This study aimed to predict the binding pose of bufadienolides from Kalanchoe pinnata on Na + /K + -ATPase using molecular docking in comparison with a known inhibitor, and to determine the important functional group of bufadienolide that is responsible for good binding. Material and methods: Docking was performed on the receptor file (PDB ID: 4RES) using AutoDock 4.2. Before docking, the complex structure of ligand-receptor was minimized using AMBER 14. The physico-chemical properties were predicted using Biovia Draw. Results: The sterical hindrance of Glu117 to the 1,3,5-orthoacetate moiety was removed after minimisation. The docking energy, Polar Surface Area (PSA) and A Log P showed good correlation with the experimental data. The 14-OH of all bufadienolides formed a hydrogen bond with Thr797. However, the energy breakdown analysis of docking result demonstrated that C1 has the highest ligand efficiency with the strongest hydrogen bond and electrostatic energies, followed by C2 and C3. The hydrogen bond from the 10-OH and the orthoacetate ring in C1 was stronger than that of 10-CH 2 OH in C2 and 10-OH in C3. Conclusion:The best activity of C1, as compared to C2 and C3, was due to the presence of 1,3,5-orthoacetate moiety, 10-CHO, 11-OH, and 14-OH. In addition, the 11-OH group appeared to decrease the toxicity of the bufadienolide by improving its selectivity to the receptor. This result is expected to be useful in the further development of bufadienolide-based inhibitor for anticancer.

Lung cancer is one of the leading causes of cancer-related deaths in the world among both men and women. Several studies in the literature report that overexpression and mutation of the epidermal growth factor receptor (EGFR) are implicated in the pathogenesis of some lung cancers. Nimotuzumab is a humanized monoclonal antibody (mAb) that inhibits EGF binding because it binds to the extracellular domain of the EGFR. Nimotuzumab requires bivalent binding for stable attachment to cellular surface, which leads to nimotuzumab selectively binding to cells that express mAbs of moderate to high EGFR levels, and this could explain its low toxicity. This property has an advantage for development of nimotuzumab as a therapeutic and diagnostic agent. Monoclonal antibodies are large in size (150 kDa), thus penetrating slowly and residing in the blood for extended periods of time (from days to weeks); their use in imaging studies can result in low signal-to-background ratios and poor image quality. A reduction in the size of the immunoglobulin molecule has also been proposed as a means for increasing tumor penetration by mAbs. Nevertheless, it is known that the penetration of mAb into tumor cell is slow, due to its high molecular weight. Therefore, mAb is not very attractive to be used for imaging diagnostic purpose because of its kinetics and potential to elicit antibody response. The objective of this research was to study the homology modeling of a simpler functional molecule based on nimotuzumab, which consists of 2 antigen-binding fragments (Fab), namely, F(ab′)2, using MODELER. The crystal structure of Fab of nimotuzumab from protein data bank was used as a template to construct the model of F(ab′)2. Molecular dynamic simulation was performed to evaluate the stability of F(ab′)2 and conformational changes of F(ab′)2 in simulation. The result showed the dynamic behavior of antigen-binding site region of F(ab′)2 throughout simulation. This result is expected to be useful in the further development of F(ab′)2 fragment nimotuzumab as a lung cancer diagnostic.

Background: Human papillomavirus (HPV)-45 genotype circulates in high percentage in Bandung area-Indonesia, after HPV-16 and HPV-18. The aim of this study was to analyse variations of major capsid (L1) HPV-45 and its phylogeny. Furthermore in silico protein structure and epitope prediction was explored. Methods: L1 gene of HPV-45 was amplified, sequenced and aligned. Phylogenetic tree had been built and compared with a complete L1 HPV-45 sequence. Structure and epitope prediction of L1 protein were then developed in silico. Results: Of 5 L1 HPV-45 sequences collected, we have detected one variant of sub lineage A2 which was considered as a new variant, and two variants of B2. Superimposition of structure of these two variants with reference showed very similar structure. Furthermore, seven amino acid substitutions were found within these L1 variants of which two substitutions might change the polarity of corresponding amino acid I329T and S383G. The S383G occurred in surface loop (HI-Loop) of new L1 HPV-45 variant. Conclusion: Similar structure of Indonesian variants indicates that amino acids variations do not affect the L1 structure. However, one substitution with altered amino acid polarity found within the area of surface loop suggests a potential impact in antibody recognition and neutralization.

The occurrences of a highly pathogenic avian influenza virus (HPAI) type A H5N1 has caused infections in millions of poultry as well as hundreds of human cases and even mortalities. Indonesia has become one of the world's highest casualty rates of H5N1 human infections, with the number of deaths was 167 from a total of 199 cases. The development of viral resistance towards the available anti-influenza drugs neuraminidase (NA) inhibitors required the discovery of new inhibitors. In the recent advance of drug discovery, natural products have been considered as one of the essential sources of medicinal agents, and Brucea javanica has been found to possess antiviral activity against H5N1 NA. Thus, this research aimed to investigate the in silico activities of compounds from B. javanica using molecular docking methods against H5N1 NA. In this study, docking-based virtual screening of compounds from B. javanica to quickly select in silico hits to be potential NA inhibitors was performed. Subsequently, the intermolecular interactions of the inhibitor compounds with the H5N1 NA were analysed to examine the most preferred interactions. The results showed that brucein G and bruceoside C were found having the lowest binding energy and most preferred interactions with H5N1 NA and therefore, can be proposed for further study as potential NA inhibitors.

LL-37 is a membrane-active antimicrobial peptide (AMP) that could disrupt the integrity of bacterial membranes due to its inherent cationic and amphipathic nature. Developing a shorter derivative of a long peptide such as LL-37 is of great interest, as it can reduce production costs and cytotoxicity. However, more detailed information about the residual interaction between LL-37 and the membrane is required for further optimization. Previously, molecular dynamics simulation using mixed all-atom and united-atom force fields showed that LL-37 could penetrate the bilayer membrane. This study aimed to perform all-atom molecular dynamics simulations, highlighting the residual interaction of LL-37 with the simplest model of the bacterial membrane, POPE:POPG (2:1), and compare its interaction with the POPC, which represents the eukaryotic membrane. The result showed leucine–leucine as the leading residues of LL-37 that first contact the membrane surface. Then, the cationic peptide of LL-37 started to penetrate the membrane by developing salt bridges between positively charged amino acids, Lys–Arg, and the exposed phosphate group of POPE:POPG, which is shielded in POPC. Residues 18 to 29 are suggested as the core region of LL-37, as they actively interact with the POPE:POPG membrane, not POPC. These results could provide a basis for modifying the amino acid sequence of LL-37 and developing a more efficient design for LL-37 derivatives.