1,721,324 research outputs found
Inhibition of Monkeypox Virus DNA Polymerase Using Moringa oleifera Phytochemicals: Computational Studies of Drug-Likeness, Molecular Docking, Molecular Dynamics Simulation and Density Functional Theory
No full textThe emergence of zoonotic monkeypox (MPX) disease, caused by the double-stranded DNA monkeypox virus (MPXV), has become a global threat. Due to unavailability of a specific small molecule drug for MPX, this study investigated Moringa oleifera phytochemicals to find potent and safe inhibitors of DNA Polymerase (DNA Pol), a poxvirus drug target due to its role in the viral life cycle. For that, 146 phytochemicals were screened through drug-likeness and molecular docking analyses. Among these, 136 compounds exhibited drug-like properties, with Gossypetin showing the highest binding affinity (- 7.8 kcal/mol), followed by Riboflavin (- 7.6 kcal/mol) and Ellagic acid (- 7.6 kcal/mol). In comparison, the control drugs Cidofovir and Brincidofovir displayed lower binding affinities, with binding energies of - 6.0 kcal/mol and - 5.1 kcal/mol, respectively. Hydrogen bonds, electrostatic and hydrophobic interactions were the main non-bond interactions between inhibitors and protein active site. The identified compounds were further evaluated using molecular dynamics simulation, density functional theory analysis and ADMET analysis. Molecular dynamics simulations conducted over 200 ns revealed that DNA Pol-Gossypetin complex was not stable, however, Riboflavin and Ellagic acid complexes showed excellent stability indicating them as better DNA Pol inhibitors. The density functional theory analysis exhibited the chemical reactivity of these inhibitor compounds. The ADMET analysis suggested that the top phytochemicals were safe and showed no toxicity. In conclusion, this study has identified Riboflavin and Ellagic acid as potential DNA Pol inhibitors to control MPXV. Further experimental assays and clinical trials are needed to confirm their activity against the disease
phytochemicals targeting EGFR: molecular docking, molecular dynamics simulation and density functional theory studies
No full textEpidermal growth factor receptor (EGFR) is a prominent target for anticancer therapy due to its role in activating several cell signaling cascades. Clinically approved EGFR inhibitors are reported to show treatment resistance and toxicity, this study, therefore, investigates Moringa oleifera phytochemicals to find potent and safe anti-EGFR compounds. For that, phytochemicals were screened based on drug-likeness and molecular docking analysis followed by molecular dynamics simulation, density functional theory analysis and ADMET analysis to identify the effective inhibitors of EGFR tyrosine kinase (EGFR-TK) domain. Known EGFR-TK inhibitors (1-4 generations) were used as control. Among 146 phytochemicals, 136 compounds showed drug-likeness, of which Delta 7-Avenasterol was the most potential EGFR-TK inhibitor with a binding energy of -9.2 kcal/mol followed by 24-Methylenecholesterol (-9.1 kcal/mol), Campesterol (-9.0 kcal/mol) and Ellagic acid (-9.0 kcal/mol). In comparison, the highest binding affinity from control drugs was displayed by Rociletinib (-9.0 kcal/mol). The molecular dynamics simulation (100 ns) exhibited the structural stability of native EGFR-TK and protein-inhibitor complexes. Further, MM/PBSA computed the binding free energies of protein complex with Delta 7-Avenasterol, 24-Methylenecholesterol, Campesterol and Ellagic acid as -154.559 ± 18.591 kJ/mol, -139.176 ± 19.236 kJ/mol, -136.212 ± 17.598 kJ/mol and -139.513 ± 23.832 kJ/mol, respectively. Non-polar interactions were the major contributors to these energies. The density functional theory analysis also established the stability of these inhibitor compounds. ADMET analysis depicted acceptable outcomes for all top phytochemicals without displaying any toxicity. In conclusion, this report has identified promising EGFR-TK inhibitors to treat several cancers that can be further investigated through laboratory and clinical tests
Portable traffic light system / Mohamad Fairuz Ahmad and Muhammad Abrar Abdul Hamid
Full text linkThis thesis is about the design and development of the prototype of portable traffic light system with one indicator display instead of three. This thesis includes the review of current traffic light system with three indicators which includes the calculation for timer of the traffic light based on the speed and the length of the vehicle. This portable traffic light prototype is not designed to be used at the junction as normal traffic light but to be used as temporary traffic flow control when a stretch of two ways road or two lanes is under circumstances of only one lane can be used. Therefore this traffic light will allow the flow of traffic in one direction alternatively. There will be only two poles of this traffic light called main pole and sub pole. Firstly, a lot of researches and surveys conducted to get as much as possible information on how to design the best prototype ever. The research also includes the study of the hardware used in the prototype. The design begins with the decision of the hardware to be used so that software can be designed afterward. The software is designed using flow chart before write the program codes using PIC assembly language. Simulation is used to help debugging the software and to ensure the success of software design. Then the real development is started with hands on activities to build the modules for the traffic light. Generally, there are five modules build. These modules are voltage regulator, controller, relay, user control panel and lastly traffic light indicator. Voltage regulator is designed using power transistor 2N3055 because the prototype consumes current more than the conventional 7805 could support. The controller used PIC18F4550 microprocessor which then connected to relay module to drive the high current to traffic light indicator module. The user control panel module is just added feature to allow user to set timer for green time of the traffic light. To satisfy the portable functionality, this prototype will run on battery
ANALISA PENYEBAB TERBAKARNYA STUFFING BOX MESIN INDUK DI KAPAL MT.GREEN GLOBAL
Full text linkINTISARI
Nuril Muhammad Abrar Fachriansyah,2020,NIT: 52155721.T, “Analisa
penyebab terbakarnya stuffing box mesin induk di kapal MT.Green Global”,
skripsi Program Studi Teknika, Progran Diploma IV, Politeknik Ilmu
Pelayaran Semarang, Pembimbing I: Nasri, MT, M.Mar E dan Pembimbing
II: Slamet Riyadi, M.Si.
Tujuan penelitian ini adalah untuk mengetahui penyebab terbakarnya
stuffing box mesin induk di kapal MT.Green Global dengan menggunakan metode
fishbone analysis dan SHEL. Peran mesin induk sebagai motor penggerak utama
kapal sangat penting, jika kerja mesin induk tidak optimal akan berdampak buruk
pada mobilitas kapal yang dapat terganggu, dengan menggunakan metode
fishbone analysis dan SHEL untuk mencari faktor-faktor apa saja yang
menyebabkan terbakarnya stuffing box mesin induk sehingga dapat ditemukan
upaya penyelesaiannya untuk menghindari terjadinya kejadian serupa di waktu
yang akan datang.
Berdasarkan hasil penelitian yang dilakukan di MT.Green Global dan
dengan menggunakan metode fault tree analysis dan SHEL menghasilkan faktorfaktor yang dapat menyebabkan terbakarnya stuffing box mesin induk adalah
masuknya hasil pembakaran ke ruang stuffing box, kotornya ruang stuffing box
underpiston akibat terlalu banyak sludge yang terakumulasi,udara pembilasan
yang kurang terdistribusi secara optimal ke seluruh silinder,serta bermasalahnya
mesin bantu penunjang kinerja mesin induk.
Hasil yang diperoleh setelah dianalisis menunjukkan bahwa pertama :
tujuan dari perawatan dan perbaikan bagian yang rusak pada mesin induk
merupakan langkah awal untuk mencegah terjadinya kebakaran pada stuffing box
dikarenakan dengan dilakukanya perawatan dan perbaikan yang rutin maka
performa mesin akan tetap terjaga, Kedua : terbakarnya stuffing box mesin induk
tidak hanya disebabkan karena faktor dalam mesin induk itu sendiri namun juga
faktor luar yang secara tidak langsung memengaruhi kinerja mesin induk dan
ketiga : perawatan pada sistem udara pembilasan juga dapat mencegah terjadinya
kebakaran pada ruang stuffing box.
ABSTRACT
Nuril Muhammad Abrar Fachriansyah, 2020, NIT: 52155721.T, "Analysis the
cause of burning in main engine stuffing box on MT.Green Global ", thesis
of study Program Teknika, Diploma IV Program, Merchant Marine
Polytechnic of Semarang, Supervisor I: Nasri, MT, M.Mar E and supervisior
II: Slamet Riyadi, M.Si.
The purpose of this research was to determine the cause of the burning of
the main engine stuffing box on the MT.Green Global using fishbone analysis and
SHEL methods. The role of the main engine as the main driving force of the ship
is very important, if the work of the main engine is not optimal it will have a
negative impact on the mobility of the ship that can be disrupted, by using the
fishbone analysis and SHEL method to look for any factors that cause the engine's
stuffing box fire so that it can a solution was found to avoid similar incidents in
the future.
Based on the results of research conducted at MT.Green Global and by
using the fault tree analysis and SHEL methods produce factors that can cause the
burning of the main engine stuffing box is the entry of the combustion results into
the stuffing box, dirty underpiston stuffing box space due to too much sludge
accumulates, less optimal distribution of flushing air to all cylinders, and
problems with supporting engines to support the main engine's performance.
The results obtained after analysis show that first: the purpose of
maintenance and repair of damaged parts on the main engine is the first step to
prevent fires in the stuffing box due to routine maintenance and repair, the engine
performance will be maintained, Second: the burning of the stuffing box The main
engine is not only caused by factors within the main engine itself but also external
factors that indirectly affect the performance of the main engine and third:
maintenance o
Estimating the human height based on foot length by using Least Squares method, Runge Kutta 4th order and cubic B spline / Muhammad Abrar Izham Ajizi
Full text linkThis study aims to estimate human height based on foot length using three different methods: Least Squares Method, Runge Kutta 4th Order, and Cubic B-spline. Data from 50 participants were collected through the Google form. The Goodness of Fit metrics, including Mean Squares Error (MSE), Root Mean Square Error (RMSE), R-squared, Adjusted R-squared, Akaike Information Criterion (AIC), and Bayesian Information Criterion (BIC) were analysed to evaluate the performance of each method. The results indicate that the Runge Kutta 4th Order method consistently outperformed the other two methods across all Goodness of Fit metrics. It achieved the lowest MSE and RMSE values, indicating superior predictive accuracy compared to the Cubic B Spline, which had the highest MSE and RMSE values. The R-squared and adjusted R-squared values for the Runge Kutta algorithm were close to 1, suggesting an excellent fit and capturing a significant proportion of the variance in the data. Furthermore, the AIC and BIC values also favoured the Runge Kutta 4th Order method, with the lowest values, indicating a better trade-off between model fit and complexity. On the other hand, the Cubic B-spline method had the highest AIC and BIC values, suggesting poor model fit or excessive complexity. In conclusion, based on the Goodness of Fit results, the Runge Kutta 4th Order method is recommended for estimating human height based on foot length. Additionally, the analysis revealed a weak positive relationship between foot length and human height, as indicated by Pearson's correlation coefficient
A computational study of the fold and stability of cytochrome c with implications for disease
Full text linkCytochrome c (Cyt-c), encoded by the CYCS gene, is crucial for electron transport, peroxidase activity, and apoptosis. Mutations in CYCS cause thrombocytopenia 4, a disorder with low platelet counts. We have, for instance, recently described six Italian families with five different heterozygous missense CYCS variants. These mutations likely enhance peroxidase and apoptotic activities, yet the mechanisms causing reduced platelet production and increased apoptosis are unclear. This study investigates clinically-related Cyt-c variants using an integrated bioinformatics approach. Our findings reveal that all variants are at evolutionarily conserved sites, potentially disrupting Cyt-c function and contributing to disease phenotypes. Specific variants are predicted to affect phosphorylation (T20I, V21G, Y49H), and ubiquitination (G42S, A52T, A52V, T103I). Molecular dynamics simulations (500 ns) revealed significant structural differences from the wild-type protein, with mutants showing reduced stability and increased unfolding and flexibility, particularly in the Ω-loops. These changes result in the displacement of the Ω-loops away from the heme iron, weakening critical hydrogen bonds and consequently opening the heme active site. This open conformation may enhance accessibility to small molecules such as H2O2, thereby promoting peroxidase activity, which may enhance apoptosis and likely impact megakaryopoiesis and platelet homeostasis in THC4
Repurposing doxycycline for the inhibition of monkeypox virus DNA polymerase: a comprehensive computational study
No full textThe global spread of monkeypox, caused by the double-stranded DNA monkeypox virus (MPXV), has underscored the urgent need for effective antiviral treatments. In this study, we aim to identify a potent inhibitor for MPXV DNA polymerase (DNAP), a critical enzyme in the virus replication process. Using a computational drug repurposing approach, we performed a virtual screening of 1615 FDA-approved drugs based on drug-likeness and molecular docking against DNAP. Among these, 1430 compounds met Lipinski's rule of five for drug-likeness, with Doxycycline emerging as the most promising competitive inhibitor, binding strongly to the DNAP active site with a binding affinity of - 9.3 kcal/mol. This interaction involved significant hydrogen bonds, electrostatic interactions, and hydrophobic contacts, with Doxycycline demonstrating a stronger affinity than established antivirals for smallpox, including Cidofovir, Brincidofovir, and Tecovirimat. Stability and flexibility analyses through a 200 ns molecular dynamics simulation and normal mode analysis confirmed the robustness of Doxycycline binding to DNAP. Overall, our results suggest Doxycycline as a promising candidate for monkeypox treatment, though additional experimental and clinical studies are needed to confirm its therapeutic potential and clinical utility. Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00307-7
Asynchronous Quadrature-Phase Undersampling Technique for Wide-Frequency Impedance Measurement
No full textAn impedance measurement (IM) technique based on asynchronous quadrature-phase undersampling is proposed to support a wide frequency range (FR) while achieving a high throughput with reduced hardware overhead. In the proposed method, a reference resistor is placed in series with the target impedance, and a sinusoidal current is injected into these. The two sinusoids from the target impedance and the reference resistor are amplified by instrumentation amplifiers (IAs) and directly sampled by an analog-to-digital converter (ADC). The magnitude and phase of each sinusoid can be calculated in the digital domain through only four samples with quadrature-phase differences. In the conventional digital demodulation design, the delay of IAs and the limited sampling frequency of the ADC, f(S), restrict the maximum FR. To address this challenge, we proposed an asynchronous sampling and processing method that can measure the magnitudes and phases of sinusoids regardless of IA's delay. Furthermore, to extend the FR beyond f(S)/2, the proposed technique employs undersampling when the frequency of the injected signal is higher than f(S)/2. As a result of these techniques, a wide FR from 10 Hz to 4.01 MHz is achieved with magnitude and phase errors of less than 0.8% and 0.8 degrees, respectively, through an ADC of a maximum f(S) of 40 kSps only. The implemented prototype shows a hardware-efficient IM design, requiring only two IAs, a microcontroller unit (MCU) with an embedded ADC, and a reference resistor. A high throughput of f(S)/8 approximate to 5 kSps can be achieved through an ADC in a time-interleaving manner.
In-silico prediction of TGF-β1 non-synonymous variants and their impact on binding affinity to Fresolimumab
No full textTGF-β1 is a potent immunoregulatory cytokine that plays diverse roles in development, bone healing, fibrosis, and cancer. However, characterizing TGF-β1 gene variants is challenging because the structural and functional consequences of these variants are still undetermined. In this study, we aimed to perform an in-silico analysis of TGF-β1 non-synonymous variants and their pathogenic effects on the TGF-β1 protein. A total of 10,252 TGF-β1 SNPs were collected from the NCBI dbSNP database and in-silico tools (SIFT, PROVEAN, Mutation Taster, ClinVar, PolyPhen-2, CScape, MutPred, and ConSurf) were used. The in-silico predicted potential variants were further investigated for their binding to the TGF-β1 targeting drug "Fresolimumab". Molecular docking was performed using HADDOCK and confirmed by PRODIGY and PDBsum. The in-silico analysis predicted four potential TGF-β1 nsSNPs: E47G in the LAP domain of the propeptide and I22T, L28F, and E35D in the mature TGF-β1 peptide. HADDOCK and molecular dynamics simulations revealed that the I22T and E35D variants have higher binding affinity for Fresolimumab as compared to the wild type and L28F variants. Molecular dynamics simulations (100 ns) and principal component analysis showed that TGF-β1 variants influenced the protein structure and caused variations in the internal dynamics of protein complexes with the antibody. Among them, the E35D variant significantly destabilized the TGF-β1 protein structure, resulting in rearrangement in the binding site and affecting the interactions with the Fresolimumab. This study identified four variants that can affect the TGF-β1 protein structure and result in functional consequences such as impaired response to Fresolimumab.Communicated by Ramaswamy H. Sarma
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