MOLECULAR DOCKING AND PHARMACOKINETIC PREDICTION OF HERBAL DERIVATIVES AS MALTASE-GLUCOAMYLASE INHIBITOR

  Objective: To perform molecular docking and pharmacokinetic prediction of momordicoside F2, beta-sitosterol, and cis-N-feruloyltyramine herbal derivatives as maltase-glucoamylase (MGAM) inhibitors for the treatment of diabetes.Methods: The herbal derivatives and standard drug miglitol were docked differently onto MGAM receptor using AutoDock Vina software. In addition, Lipinski's rule, drug-likeness, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were analyzed using Molinspiration, ADMET structure–activity relationship, and prediction of activity spectra for substances online tools.Results: Docking studies reveal that momordicoside F2, beta-sitosterol, and cis-N-feruloyltyramine derivatives have high binding affinity to the MGAM receptor (−7.8, −6.8, and −6.5 Kcal/Mol, respectively) as compared to standard drug miglitol (−5.3 Kcal/Mol). In addition, all the herbal derivatives indicate good bioavailability (topological polar surface area <140 Ȧ and Nrot <10) without toxicity or mutagenic effects.Conclusion: The molecular docking and pharmacokinetic information of herbal derivatives obtained in this study can be utilized to develop novel MGAM inhibitors having antidiabetic potential with better pharmacokinetic and pharmacodynamics profile

In Silico Analysis of Glucose Oxidase H516r and H516d Mutations for an Enzymatic Fuel Cell

Glucose oxidase (GOx) is an oxido-reductase enzyme that catalyzes glucose into hydrogen peroxide and glucono delta-lactone (GDL). GOx has the potential to be used in the medical field. Numerous research concerning the usage of GOx to create enzymatic biofuel cells have been done, nevertheless the results obtained have not been optimal. This research aims to increase the Km values of GOx in order to increase its potential as a material for an enzymatic fuel cell. The amino acid histidine in position 516 is a residue in the active site that plays an important part in the process of glucose oxidation. In this research we mutated H516 by in silico twice resulting in the mutants R516 and D516. The mutations resulted in a change of the docking area for both mutants and in the docking affinity for H516D resulting in higher Km values. This shows that the H516 residue plays an important part in the functions of glucose oxidase and mutation into aspartate could improve glucose oxidase based enzymatic fuel cells

Potential Indonesian Natural Compound as antiviral for COVID-19 targeting the RdRp: In silico Study

Research related to SARS-CoV-2 drugs is still ongoing. In this initial research, we perform a computational approach on SARS-CoV-2 inhibitors. RNA-dependent RNA polymerase (RdRp) is one of the functional proteins in SARS-CoV-2 that can be a target for drug development, which has an essential function in the viral replication process synthesizing the RNA genome of the virus. This study used the RdRp-Remdesivir complex structure from RCSB with ID PDB 7BV2, with a resolution of 2.5 Å. Currently, Remdesivir is under the clinical trial phase as a Covid-19 drug. In this study, we tested a thousand natural Indonesian compounds used as SARS-CoV-2 RdRp inhibitors obtained from the Indonesian natural compounds database (HerbalDB). The first stage of this computational analysis was pharmacophore modeling structure-based drug design. The natural compounds were analyzed based on their steric and electronic similarities to Remdesivir. A molecular docking simulation was then performed to obtain binding energy and bond stability to produce natural compounds that can inhibit RdRp SARS-CoV-2. The final stage was the molecular dynamics simulation that explored the conformational space of natural compounds and proteins. The ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) test was carried out on the five best compounds to obtain these natural compounds' computational pharmacology and pharmacokinetics. The simulation identified Sotetsuflavone (CID: 5494868) from Cycas revoluta, Grossamide (CID: 5322012) from Cannabis sativa, and 6-Hydroxyluteolin-6,7-disulfate (CID: 13845917) from Lippia nodiflora are the best compounds that can inhibit RdRp SARS-CoV-2. These potential compounds can then be tested in-vitro and in-vivo in the future. &nbsp

Molecular Interaction Analysis of COX-2 against Curcuminoid and Xanthorizol Ligand as Anti Breast Cancer using Molecular Docking

Breast cancer is one of the most common cancer in the world that occurs in women. Thedevelopment process of cancer is regulated by a variety of pathways that involve various enzymes. COX-2 is an enzyme involved in the inflammatory process in further stages that will play importantroles in breast cancer cells progression. The uses of natural compound from plants give new hope forbreast cancer treatment with minimal side effects. Temulawak is a potential breast cancer drugs because it contains curcuminoid and xanthorizol. Curcumin and xanthorizol has been reported to have chemopreventive effect on colon cancer development. The drug that has same functions of these compounds needed to be examined with various approaches. One of the approach used in this research is molecular docking. Based on ligand analysis with Lipinski and toxicity test using ADMET, curcuminoid and xanthorizol met criteria as medicinal compounds. Curcumin had the highest binding affinity(?G) with the value -9.3 kcal/mol but still under commercial drug celecoxib binding affinity (?G) = -12,5. There were three hydrogen bonds in amino acid Arg106 and Tyr341 His75 which were amino acids in the active side of COX-2. There were 15 amino acids that have similar ties with commercial drug celecoxib. Based on the binding affinity and binding similiarity, curcuminoid and xanthorizol were predicted as compounds that have potential as competitive inhibitor of COX-2 enzyme

Simulasi Docking Senyawa Kurkumin dan Analognya Sebagai Inhibitor Reseptor Androgen pada Kanker Prostat

Curcumin, the major compound of Curcuma longa L, has been proven to have the toxicity effect on prostate cancer cell. This research was aimed to study the affinity and interaction of curcumin and its analogs as compettitive inhibitor to androgen hormon before working in vitro/in vivo research. Curcumin and its analogs were transformed into 3D structure, then docked to androgen receptor (3B67). The data of Gibbs energy (?G) value showed stability interaction between ligand and androgen receptor residues. The docking results showed that curcumin and its analogs have potential as inhibitor on androgen receptor. Based on results ?G score, analog 4 (1,7-bis-(3,4-dihydroxy-phenyl)-hepta-1,6-diene-3,5-dione) has highest potential as the inhibitor for androgen receptor

In-Silico Design of Novel Glucagon-Like Peptide 1 Mutants as Candidate for New Peptide Agonist Drugs

The binding of glucagon-like peptide 1 (GLP-1) incretin hormone and its receptor GLP-1R plays an important role in the human body. The GLP-1 acts as the insulin secretion stimulator through a GLP-1R agonist activation to avoid the type 2 diabetes mellitus problem. A recent development in computational sciences has enabled us to design a new GLP-1 mutant which has a better binding stability to GLP-1R. In this paper, we have conducted an in-depth analysis of protein-protein docking of GLP-1 and GLP-1R receptor to determine the responsible factors affecting the binding stability. The protein-protein binding stability was analyzed by performing the point mutations on the GLP-1 structure and running the molecular dynamics simulation of the docked structures. Five mutants, Lys20Arg, Lys20His, Lys20Ser, Lys20Gly, and Lys20Ala, has been created computationally and docked with GLP-1R and tested via a molecular dynamics simulation and the free energy perturbation calculation to search for the best-binding mutant. Our results have shown that the Lys20His mutant design has the best potential to be developed as a new peptide agonist drug based on its binding affinity and structural integrity as compared to other mutants and the peptide agonist drugs available in the market exenatide, and liraglutide

Thermodynamics of pairing in mesoscopic systems

Using numerical and analytical methods implemented for different models we conduct a systematic study of thermodynamic properties of pairing correlation in mesoscopic nuclear systems. Various quantities are calculated and analyzed using the exact solution of pairing. An in-depth comparison of canonical, grand canonical, and microcanonical ensemble is conducted. The nature of the pairing phase transition in a small system is of a particular interest. We discuss the onset of discontinuity in the thermodynamic variables, fluctuations, and evolution of zeros of the canonical and grand canonical partition functions in the complex plane. The behavior of the Invariant Correlational Entropy is also studied in the transitional region of interest. The change in the character of the phase transition due to the presence of magnetic field is discussed along with studies of superconducting thermodynamics.Comment: 19 pages, 24 figure

Modeling the Output Performance of Al_0.3Ga_0.7As/InP/Ge Triple-Junction Solar Cells for a Venus Orbiter Space Station

The performance of Al0.3Ga0.7As/InP/Ge triple-junction solar cells (TJSC) at the geosynchronous orbit of Venus had been simulated in this paper by assuming that the solar cells were put on a hypothetical Venus orbiter space station. The incoming solar radiation on TJSC was calculated by a blackbody radiation formula, while PC1D program simulated the electrical output performance. The results show that the incoming solar intensity at the geosynchronous orbit of Venus is 3000 W/m2, while the maximum solar cell efficiency achieved is 38.94%. Considering a similar area of the solar panel as the International Space Station (about 2500 m2), the amount of electricity produced by Venus orbiter space station at the geosynchronous orbit of Venus is 2.92 MW, which is plenty of energy to power the space station for long-term exploration and intensive research on Venus

The Role of E27-K31 and E56-K10 Salt-Bridge Pairs in the Unfolding Mechanism of the B1 Domain of Protein G

Molecular dynamics simulations of the B1 fragment of protein G (56 residues) have been performed at 325, 350, 375, 400, 450 and 500 K for 10 ns. An analysis of its structural and energetic parameters has indicated that the unfolding process of the GB1 protein begins at 900 ps of a 500-K simulation. The unfolding process is initiated when hydrogen bonds in the hydrophobic core region are broken; it continues with the α-helix transformation into coils and turns and ends with the destruction of the β-hairpins. These unfolding events are consistent with the hybrid model of the protein folding/unfolding mechanism, which is a compromise between the hydrophobic core collapse model and the zipper model. Salt-bridge pairs were found to play an important role in the unfolding process by maintaining the integrity of the tertiary structure of the protein. The breaking (or disappearance) of the salt-bridge pairs E27–K31 (in the α-helix) and E56–K10 (connecting β4 and β1) has resulted in the destruction of secondary structures and indicates the beginning of the unfolding process. Our results also suggest that the unfolding process in this simulation was not a complete denaturation of the protein because some β-hairpins remaine

PAIRING CORRELATIONS AND PHASE TRANSITIONS IN MESOSCOPIC SYSTEMS

The Office of Graduate Studies has verified and approved the above named committee members