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1.
One Health ; 18: 100685, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39010965

ABSTRACT

Transmission of extended-spectrum ß-lactamase (ESBL) genes has increased the global prevalence of ESBL-producing bacteria, especially in developing countries. Human infection with these bacteria may be food-mediated but has not been fully elucidated. Therefore, we aimed to examine ESBL-producing bacteria in edible river fish and elucidate their potential for horizontal gene transfer. A total of 173 ESBL-producing Enterobacterales were isolated (Escherichia coli [n = 87], Klebsiella pneumoniae [n = 52], Enterobacter cloacae complex [n = 18], Citrobacter freundii complex [n = 14], Atlantibacter hermannii [n = 1] and Serratia fonticola [n = 1]) from 56 of 80 fish intestinal contents sampled. Among the bacterial bla CTX-M genotypes, bla CTX-M-55 was the most predominant, followed by bla CTX-M-15, bla CTX-M-27, and bla CTX-M-65. Furthermore, we found that ESBL-producing Enterobacterales were able to transfer their bla CTX-M genes to E. coli. In summary, our results suggest that ESBL-producing Enterobacterales transfer bla CTX-M to indigenous gut E. coli in humans, following the consumption of contaminated fish.

2.
Microbiol Resour Announc ; 13(6): e0005624, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38682768

ABSTRACT

Extended-spectrum ß-lactamase-producing Atlantibacter hermannii was isolated from an edible river fish, Anabas testudineus, which was sold in a market located in Vietnam. The genome sequence was obtained by using next-generation sequencing, which involved Oxford Nanopore and Illumina technologies. The 92 kb plasmid encodes the gene blaCTX-M-27.

3.
Microbiol Resour Announc ; 13(3): e0122623, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38358276

ABSTRACT

Extended-spectrum ß-lactamase-producing non-O1 Vibrio cholerae was isolated from edible Mastacembelus sp. in Vietnam. The genome sequence was sequenced using DNBSEQ-G400 and MinION Mk1b. A plasmid of approximately 183-kb encoding blaCTX-M-55 and blaTEM-1 was detected.

4.
Mar Pollut Bull ; 198: 115812, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38043208

ABSTRACT

The spread of antibiotic-resistant bacteria is a global problem that should be addressed through the perspective of the "one health" concept. The purpose of this study was to determine the contamination rate of antibiotic-resistant Aeromonas spp. in fresh water river fish purchased from a fish market in Vietnam. We then defined the pattern of antibiotic resistance to assess antibiotic-resistant contamination. Antibiotic-resistant Aeromonas spp. were detected in the intestinal contents of 32 of 80 fish. blaNDM-1 was detected in seven strains. Extended-spectrum ß-lactamase and AmpC ß-lactamase-related genes were detected in 28 strains, including blaCTX-M-55, blaCTX-M-15, blaCTX-M-1, and blaDHA,blaFOX, and blaMOX. The blaNDM-1 detected in the seven Aeromonas spp. strains were found chromosomally. This finding suggests that the blaNDM gene is stable in the natural environment and may spread widely into animals and humans via Aeromonas spp. with a transposon. Our results suggest the importance of continuing to monitor carbapenemase genes in Aeromonas spp. to evaluate the possibility that they may spread in other Enterobacterales, and to elucidate the mechanism of spread.


Subject(s)
Aeromonas , Humans , Animals , Aeromonas/genetics , Gastrointestinal Contents , Vietnam , beta-Lactamases/genetics , Bacterial Proteins/genetics , Anti-Bacterial Agents/pharmacology , Fishes/genetics , Fresh Water , Chromosomes , Microbial Sensitivity Tests
5.
Microbiol Resour Announc ; 12(7): e0014923, 2023 Jul 18.
Article in English | MEDLINE | ID: mdl-37367473

ABSTRACT

Salmonella enterica SE20-C72-2 and Escherichia coli EC20-C72-1 were isolated from the edible fish Anabas testudineus in Vietnam. The chromosomes and plasmids from both strains were sequenced using Oxford Nanopore and Illumina sequencing. Plasmids approximately 250 kbp long, encoding blaCTX-M-55 and mcr-1.1, were detected in both strains.

6.
Microbiol Resour Announc ; 12(5): e0134422, 2023 May 17.
Article in English | MEDLINE | ID: mdl-37010426

ABSTRACT

Carbapenem-resistant Citrobacter freundii CF20-4P-1 and Escherichia coli EC20-4B-2 were isolated from edible Mastacembelidae in Vietnam. We present the draft genome sequences, and the complete plasmid genome sequencing was also performed by hybrid assembly sequencing of Oxford Nanopore and Illumina. The 137-kbp plasmid encoding the assembled blaNDM-1 was detected in both strains.

7.
G3 (Bethesda) ; 13(5)2023 05 02.
Article in English | MEDLINE | ID: mdl-36881928

ABSTRACT

The asymmetric increase in average nighttime temperatures relative to increase in average daytime temperatures due to climate change is decreasing grain yield and quality in rice. Therefore, a better genome-level understanding of the impact of higher night temperature stress on the weight of individual grains is essential for future development of more resilient rice. We investigated the utility of metabolites obtained from grains to classify high night temperature (HNT) conditions of genotypes, and metabolites and single-nucleotide polymorphisms (SNPs) to predict grain length, width, and perimeter phenotypes using a rice diversity panel. We found that the metabolic profiles of rice genotypes alone could be used to classify control and HNT conditions with high accuracy using random forest or extreme gradient boosting. Best linear unbiased prediction and BayesC showed greater metabolic prediction performance than machine learning models for grain-size phenotypes. Metabolic prediction was most effective for grain width, resulting in the highest prediction performance. Genomic prediction performed better than metabolic prediction. Integrating metabolites and genomics simultaneously in a prediction model slightly improved prediction performance. We did not observe a difference in prediction between the control and HNT conditions. Several metabolites were identified as auxiliary phenotypes that could be used to enhance the multi-trait genomic prediction of grain-size phenotypes. Our results showed that, in addition to SNPs, metabolites collected from grains offer rich information to perform predictive analyses, including classification modeling of HNT responses and regression modeling of grain-size-related phenotypes in rice.


Subject(s)
Oryza , Temperature , Oryza/genetics , Hot Temperature , Edible Grain/genetics , Phenotype , Genomics
8.
Trauma Violence Abuse ; 24(3): 1712-1726, 2023 07.
Article in English | MEDLINE | ID: mdl-35343325

ABSTRACT

Perinatal domestic violence (P-DV) is a common form of violence experienced by women and is associated with adverse impacts on their own physical and mental health and that of their offspring. Illuminating the risk factors for, potential effects of, and promising interventions to reduce P-DV is essential for informing policies to tackle P-DV and mitigate its negative impacts. This umbrella review of recent high-quality systematic reviews and meta-analyses of worldwide research on P-DV provides a systematic synthesis of current knowledge relating to the prevalence, risk factors for, possible outcomes of and interventions to reduce and prevent P-DV. 13 reviews identified through systematic searches of computerised databases, manual search and expert consultation met our inclusion criteria (i.e. English systematic reviews and/or meta-analyses that were from recent 10 years, focused on women exposed to P-DV, assessed risk factors, possible outcomes and/or interventions, and were of fair to high methodological quality). Our results suggest that while there is a growing understanding of risk factors and possible outcomes of P-DV, this knowledge has thus far not been translated well into effective interventions. P-DV intervention programmes that have been subject to rigorous evaluation are mostly relatively narrow in scope and could benefit from targeting a wider range of maternal and child wellbeing outcomes, and perpetrator, relationship and community risk factors. The overall quality of the evidence syntheses in this field is reasonable; however, future studies should involve multiple reviewers at all key stages of systematic reviews and meta-analyses to help enhance reliability.


Subject(s)
Domestic Violence , Female , Humans , Pregnancy , Domestic Violence/prevention & control , Prevalence , Reproducibility of Results , Risk Factors , Systematic Reviews as Topic
9.
Front Microbiol ; 13: 987801, 2022.
Article in English | MEDLINE | ID: mdl-36246267

ABSTRACT

Hand, foot, and mouth disease (HFMD) is a common infection that primarily affects children in preschool and kindergarten; however, there is yet no vaccination or therapy available. Despite the fact that current research is only focused on numerous strains of Enterovirus-A71 (EV-A71) 3C protease (3Cpro), these investigations are entirely separate and unrelated. Antiviral agents must therefore be tested on several EV strains or mutations. In total, 21 previously reported inhibitors were evaluated for inhibitory effects on eight EV-A71 3Cpro, including wild-type and mutant proteins in this study, and another 29 powerful candidates with inhibitory effects on EV-A71 were investigated using the molecular docking approach. This method is to determine the broad-spectrum of the antiviral agents on a range of strains or mutants because the virus frequently has mutations. Even though Rupintrivir is reported to pass phase I clinical trial, 4-iminooxazolidin-2-one moiety (FIOMC) was shown to have a broader anti-3Cpro spectrum than Rupintrivir. Meanwhile, Hesperidin possessed a better 3Cpro inhibitory capability than FIOMC. Thus, it could be considered the most promising candidate for inhibiting various strains of EV-A71 3Cpro proteins in the newly anti-EV compounds group. Furthermore, the mutation at E71A has the most significant impact on the docking results of all ligands evaluated. Future in vitro experiments on Hesperidin's ability to inhibit 3Cpro activity should be conducted to compare with FIOMC's in vitro results and validate the current in silico work.

10.
Mar Pollut Bull ; 184: 114108, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36166861

ABSTRACT

The threat of antimicrobial resistance is increasing. Microbial food contamination poses a serious public health risk; however, there are only a few studies on the prevalence of colistin-resistant Escherichia coli (COL-E) contamination in freshwater fish. This study aimed to characterise the antibiotic resistance genes and antibiotic susceptibility profiles of COL-E in freshwater fish in Vietnam. In total, 103 fish were collected and 63 COL-E were isolated. COL-E was investigated by genotyping mcr and AmpC/extended-spectrum ß-lactamase (ESBL)-related genes. The results show that COL-E and AmpC/ESBL-producing COL-E were confirmed in 24.3 % and 14.6 % of the fish, respectively. Multiplex PCR for mcr-1-9 showed that all 63 COL-E harboured mcr-1, while mcr-3 was detected in 7.9 % of COL-E. The minimum inhibitory concentration of colistin ranged from 2 to 256 µg/mL. Meanwhile, antibiotic susceptibility results show that all COL-E were resistant to ampicillin, streptomycin, and chloramphenicol.


Subject(s)
Escherichia coli Infections , Escherichia coli Proteins , Animals , Colistin/pharmacology , Escherichia coli , Escherichia coli Proteins/genetics , beta-Lactamases/genetics , Drug Resistance, Bacterial/genetics , Plasmids , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Fresh Water , Ampicillin , Streptomycin , Chloramphenicol/analysis
11.
Sci Total Environ ; 852: 158203, 2022 Dec 15.
Article in English | MEDLINE | ID: mdl-36044953

ABSTRACT

Sulfur (S) is a crucial component in the environment and living organisms. This work is the first attempt to provide an overview and critical discussion on the roles, mechanisms, and environmental applications of sulfur-oxidizing bacteria (SOB). The findings reveal that key enzymes of SOB embarked on oxidation of sulfide, sulfite, thiosulfate, and elemental S. Conversion of reduced S compounds was oxidatively catalyzed by various enzymes (e.g. sulfide: quinone oxidoreductase, flavocytochrome c-sulfide dehydrogenase, dissimilatory sulfite reductase, heterodisulfide reductase-like proteins). Environmental applications of SOB discussed include detoxifying hydrogen sulfide, soil bioremediation, and wastewater treatment. SOB producing S0 engaged in biological S soil amendments (e.g. saline-alkali soil remediation, the oxidation of sulfide-bearing minerals). Biotreatment of H2S using SOB occurred under both aerobic and anaerobic conditions. Sulfide, nitrate, and sulfamethoxazole were removed through SOB suspension cultures and S0-based carriers. Finally, this work presented future perspectives on SOB development, including S0 recovery, SOB enrichment, field measurement and identification of sulfur compounds, and the development of mathematical simulation.


Subject(s)
Hydrogen Sulfide , Biodegradation, Environmental , Hydrogensulfite Reductase/metabolism , Thiosulfates , Nitrates/metabolism , Sulfur/metabolism , Bacteria/metabolism , Oxidation-Reduction , Oxidoreductases/metabolism , Sulfides/metabolism , Soil , Sulfamethoxazole/metabolism , Sulfites/metabolism , Alkalies , Quinones
12.
ANZ J Surg ; 92(4): 712-717, 2022 04.
Article in English | MEDLINE | ID: mdl-35041241

ABSTRACT

BACKGROUND: Surgical departments have been dramatically impacted by the novel coronavirus 19 (COVID-19) pandemic, with the cancellation of elective cases and changes to the provision of emergency surgical care. The aim of this study was to determine whether structural changes made within our facility's surgical department during COVID-19 altered National Emergency Access Target (NEAT) times and impacted on patient outcomes. METHODS: Emergency surgical cases over a 4-month time period were retrospectively collected and statistically analysed, divided into pre- and mid-COVID-19 pandemic. RESULTS: Baseline characteristics between the groups were comparable. There was a significant increase in consultant presence in theatre in the COVID group. There were also statistically significant reductions in NEAT times at each timepoint, although these did not meet national guidelines. There was no change in emergency surgical workload, complication rate or mortality rates within 30 days. CONCLUSION: Any significant change to services requires a coordinated hospital-wide approach, not just from a single department, and clinicians must continue to be wary of benchmarked times as the overall feasibility and safety of NEAT times has also been highlighted again.


Subject(s)
COVID-19 , Pandemics , COVID-19/epidemiology , Emergency Service, Hospital , Hospitals , Humans , Retrospective Studies
13.
Arch Microbiol ; 204(2): 137, 2022 Jan 15.
Article in English | MEDLINE | ID: mdl-35032196

ABSTRACT

Although the spread of plasmid-mediated antibiotic-resistant bacteria is a public health concern, food contamination with plasmid-mediated antibiotic-resistant Escherichia coli in Vietnam has not been well investigated. This study aimed to describe the prevalence of colistin-resistant, carbapenem-resistant, and endemic blaCTX-M in extended-spectrum ß-lactamase (ESBL) producing E. coli isolates. Colistin and carbapenem-resistant ESBL-producing E. coli were isolated from chickens in Vietnam and Japan. Colistin-resistant and AmpC/ESBL-producing E. coli (52% and 93%, respectively) were detected in chickens from Vietnam, in comparison to 52.7%, AmpC/ESBL-producing E. coli found in chicken from Japan. Carbapenem-resistant E. coli has not been isolated in Vietnam and Japan. Genotyping revealed that colistin-resistant E. coli harboured mcr-1, and most of the AmpC/ESBL-related genes were blaCTX-M-55 and blaCTX-M-65 together with blaTEM in Vietnamese chickens and blaCMY-2 in Japanese chickens. Multi-drug resistance analysis showed that ESBL-producing E. coli isolates had greater resistance to quinolones, streptomycin, and chloramphenicol than colistin-resistant E. coli isolates from Vietnam, suggesting the selection of multiple antibiotic resistance genes in ESBL-producing E. coli. In conclusion, colistin-resistant E. coli was detected in approximately half of the chicken samples, the majority of which harboured mcr-1. The high prevalence of ESBL-producing E. coli has remained constant in the last 5 years. The predominant blaCTX-M in ESBL-producing E. coli was blaCTX-M-55 or blaCTX-M-65, with the coexistence of blaTEM in Vietnam. These results can be implemented in monitoring systems to overcome the development of antimicrobial resistance.


Subject(s)
Escherichia coli Infections , Escherichia coli Proteins , Animals , Anti-Bacterial Agents/pharmacology , Chickens , Colistin/pharmacology , Escherichia coli/genetics , Escherichia coli Infections/veterinary , Escherichia coli Proteins/genetics , Meat , Plasmids/genetics , Vietnam , beta-Lactamases/genetics
14.
Sci Rep ; 11(1): 23541, 2021 12 07.
Article in English | MEDLINE | ID: mdl-34876635

ABSTRACT

Sentiment classification, which uses deep learning algorithms, has achieved good results when tested with popular datasets. However, it will be challenging to build a corpus on new topics to train machine learning algorithms in sentiment classification with high confidence. This study proposes a method that processes embedding knowledge in the ontology of opinion datasets called knowledge processing and representation based on ontology (KPRO) to represent the significant features of the dataset into the word embedding layer of deep learning algorithms in sentiment classification. Unlike the methods that lexical encode or add information to the corpus, this method adds presentation of raw data based on the expert's knowledge in the ontology. Once the data has a rich knowledge of the topic, the efficiency of the machine learning algorithms is significantly enhanced. Thus, this method is appliable to embed knowledge in datasets in other languages. The test results show that deep learning methods achieved considerably higher accuracy when trained with the KPRO method's dataset than when trained with datasets not processed by this method. Therefore, this method is a novel approach to improve the accuracy of deep learning algorithms and increase the reliability of new datasets, thus making them ready for mining.

15.
Clin Appl Thromb Hemost ; 27: 10760296211037920, 2021.
Article in English | MEDLINE | ID: mdl-34514865

ABSTRACT

Controversy persists regarding the safety and efficacy of an accelerated low-dose recombinant tissue-type plasminogen activator (rt-PA) regimen for reperfusion therapy in acute pulmonary embolism. This study describes the outcomes of an accelerated low-dose rt-PA regimen for the treatment of acute pulmonary embolism in Vietnamese patients. This was a case series from October 2014 to October 2020 from 9 hospitals across Vietnam. Patients presenting with acute pulmonary embolism with high to intermediate mortality risk were administered alteplase 0.6 mg per kilogram (maximum of 50 mg) over 15 min. The main outcomes were the proportion who survived to hospital discharge and at 3 months as well as in-hospital hemorrhage (major and minor according to International Society of Thrombosis and Hemhorrage definitions). A total of 80 patients were enrolled: 48 (60%) with high risk for mortality and 32 patients (40%) with intermediate risk for mortality. A total of 7 (8.8%) died in hospital. All deaths occurred in the high-risk mortality group. The 73 patients who were discharged alive remained alive at 3 months follow up. During hospitalization, 1 patient (1.3%) suffered major bleeding, and 7 (8.8%) had minor bleeding. An accelerated thrombolytic regimen with alteplase 0.6 mg/kg (maximum of 50 mg) over 15 min for acute pulmonary embolism appeared be effective and safe in a case series of Vietnamese patients.


Subject(s)
Fibrinolytic Agents/therapeutic use , Pulmonary Embolism/complications , Reperfusion/methods , Tissue Plasminogen Activator/therapeutic use , Acute Disease , Aged , Aged, 80 and over , Cohort Studies , Female , Fibrinolytic Agents/pharmacology , Humans , Male , Middle Aged , Pulmonary Embolism/mortality , Survival Analysis , Tissue Plasminogen Activator/pharmacology
16.
PLoS One ; 16(7): e0254012, 2021.
Article in English | MEDLINE | ID: mdl-34264966

ABSTRACT

BACKGROUND: In response to the spread of the coronavirus disease 2019 (COVID-19), plenty of control measures were proposed. To assess the impact of current control measures on the number of new case indices 14 countries with the highest confirmed cases, highest mortality rate, and having a close relationship with the outbreak's origin; were selected and analyzed. METHODS: In the study, we analyzed the impact of five control measures, including centralized isolation of all confirmed cases, closure of schools, closure of public areas, closure of cities, and closure of borders of the 14 targeted countries according to their timing; by comparing its absolute effect average, its absolute effect cumulative, and its relative effect average. RESULTS: Our analysis determined that early centralized isolation of all confirmed cases was represented as a core intervention in significantly disrupting the pandemic's spread. This strategy helped in successfully controlling the early stage of the outbreak when the total number of cases were under 100, without the requirement of the closure of cities and public areas, which would impose a negative impact on the society and its economy. However, when the number of cases increased with the apparition of new clusters, coordination between centralized isolation and non-pharmaceutical interventions facilitated control of the crisis efficiently. CONCLUSION: Early centralized isolation of all confirmed cases should be implemented at the time of the first detected infectious case.


Subject(s)
COVID-19/prevention & control , Patient Isolation/statistics & numerical data , Quarantine/statistics & numerical data , COVID-19/transmission , Disease Notification/statistics & numerical data , Disease Transmission, Infectious/statistics & numerical data , Humans , Models, Statistical
17.
Evol Bioinform Online ; 17: 11769343211003082, 2021.
Article in English | MEDLINE | ID: mdl-33795930

ABSTRACT

A high level of mutation enables the influenza A virus to resist antibiotics previously effective against the influenza A virus. A portion of the structure of hemagglutinin HA is assumed to be well-conserved to maintain its role in cellular fusion, and the structure tends to be more conserved than sequence. We designed peptide inhibitors to target the conserved residues on the HA surface, which were identified based on structural alignment. Most of the conserved and strongly similar residues are located in the receptor-binding and esterase regions on the HA1 domain In a later step, fragments of anti-HA antibodies were gathered and screened for the binding ability to the found conserved residues. As a result, Methionine amino acid got the best docking score within the -2.8 Å radius of Van der Waals when it is interacting with Tyrosine, Arginine, and Glutamic acid. Then, the binding affinity and spectrum of the fragments were enhanced by grafting hotspot amino acid into the fragments to form peptide inhibitors. Our peptide inhibitor was able to form in silico contact with a structurally conserved region across H1, H2, and H3 HA, with the binding site at the boundary between HA1 and HA2 domains, spreading across different monomers, suggesting a new target for designing broad-spectrum antibody and vaccine. This research presents an affordable method to design broad-spectrum peptide inhibitors using fragments of an antibody as a scaffold.

18.
PLoS One ; 15(12): e0239112, 2020.
Article in English | MEDLINE | ID: mdl-33382708

ABSTRACT

Influenza virus A is a significant agent involved in the outbreak of worldwide epidemics, causing millions of fatalities around the world by respiratory diseases and seasonal illness. Many projects had been conducting to investigate recovered infected patients for therapeutic vaccines that have broad-spectrum activity. With the aid of the computational approach in biology, the designation for a vaccine model is more accessible. We developed an in silico protocol called iBRAB to design a broad-reactive Fab on a wide range of influenza A virus. The Fab model was constructed based on sequences and structures of available broad-spectrum Abs or Fabs against a wide range of H1N1 influenza A virus. As a result, the proposed Fab model followed iBRAB has good binding affinity over 27 selected HA of different strains of H1 influenza A virus, including wild-type and mutated ones. The examination also took by computational tools to fasten the procedure. This protocol could be applied for a fast-designed therapeutic vaccine against different types of threats.


Subject(s)
Antibodies, Viral/chemistry , Antigens, Viral/chemistry , Drug Design , Hemagglutinin Glycoproteins, Influenza Virus/chemistry , Immunoglobulin Fab Fragments/chemistry , Influenza A Virus, H1N1 Subtype/immunology , Influenza, Human/prevention & control , Amino Acid Sequence , Antibodies, Viral/genetics , Antigens, Viral/genetics , Antigens, Viral/immunology , Binding Sites , Computer Simulation , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Humans , Immunoglobulin Fab Fragments/genetics , Influenza Vaccines/administration & dosage , Influenza Vaccines/biosynthesis , Influenza, Human/immunology , Influenza, Human/virology , Molecular Docking Simulation , Protein Binding , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Protein Interaction Domains and Motifs , Sequence Alignment , Sequence Homology, Amino Acid , Thermodynamics
19.
Evol Bioinform Online ; 15: 1176934319876938, 2019.
Article in English | MEDLINE | ID: mdl-31555044

ABSTRACT

Influenza A has caused several deadly pandemics throughout human history. The virus is often resistant to developed treatments because of its genetic drift or shift property. Broad-spectrum antibodies show a promising potential to overcome the resistance of influenza viruses. In silico studies on broad-reactive antibodies and their interactions with hemagglutinins might shed light on the rational design of a universal vaccine. In this study, 11 broad-spectrum antibodies (or antigen-binding fragments) and 14 hemagglutinins of H3N2 and H5N1 strains were docked and analyzed to provide information about the construction of the scaffold for using universal antibodies against the influenza A virus. Antigen-binding fragments that have high number of appearances in the top 3 within each H3 and H5 subtypes were chosen for protein-protein interaction analysis. The results show that while the hydrogen bond is important for Ab/Fab binding to H3, the H5-Ab/Fab system may need cation-pi interaction for a strong interaction.

20.
J Chem Inf Model ; 58(8): 1473-1482, 2018 08 27.
Article in English | MEDLINE | ID: mdl-29975531

ABSTRACT

Conventional de novo drug design is time consuming, laborious, and resource intensive. In recent years, emerging in silico approaches have been proven to be critical to accelerate the process of bringing drugs to market. Molecular dynamics (MD) simulations of single molecule and molecular complexes have been commonly applied to achieve accurate binding modes and binding energies of drug-receptor interactions. A derivative of MD, namely, steered molecular dynamics (SMD), has been demonstrated as a promising tool for rational drug design. In this paper, we review various studies over the last 20 years using SMD simulations, thus paving the way to determine the relationship between protein structure and function. In addition, the paper highlights the use of SMD simulation for in silico drug design. We also aim to establish an understanding on the key interactions which play a crucial role in the stabilization of peptide-ligand interfaces, the binding and unbinding mechanism of the ligand-protein complex, the mechanism of ligand translocating via membrane, and the ranking of different ligands on receptors as therapeutic candidates.


Subject(s)
Computer-Aided Design , Drug Design , Molecular Dynamics Simulation , Proteins/metabolism , Animals , Drug Evaluation, Preclinical , Humans , Ligands , Protein Binding , Proteins/chemistry
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