scholarly journals The design of bioactive marine peptides as a HIV-1 protease inhibitor

2021 ◽  
Vol 17 (2) ◽  
pp. 160-171
Author(s):  
Taufik Muhammad Fakih ◽  
Mentari Luthfika Dewi
Keyword(s):  
Protease Inhibitor ◽  
Molecular Interactions ◽  
In Silico ◽  
Bioactive Peptides ◽  
Bioactive Peptide ◽  
Human Immune System ◽  
Discovery Studio ◽  
Peptide Molecule ◽  
Immunodeficiency Syndrome ◽  
Hiv 1

Background: Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV or AIDS) is a disease related to the human immune system. Given its important role in viral replication, HIV1 protease (HIV1 PR) becomes the major therapeutic target in the treatment of AIDS. In this case, we need a dynamic aspect of molecular interactions that can demonstrate the important role of conformational variability in the design of HIV1 PR inhibitors. There are several inhibitor candidates from marine organisms, such as the LLEYSL and LLEYSI bioactive peptides produced by oysters (Crassostrea gigas). Objective: Proteinpeptide docking method was used in silico to identify, evaluate, and explore the molecular interactions between bioactive peptide molecules and HIV-1 protease macromolecules. Methods: The sequencing of bioactive peptide molecules was modeled into 3D conformation using the PEPFOLD software. The best conformation was chosen for the study of molecular interactions against HIV1 protease macromolecules using the PatchDock software. The molecular interactions formed were further observed using the BIOVIA Discovery Studio 2020 software. Results: The results of this study indicated that the LLEYSL bioactive peptide had the best affinity with an ACE score of minus 1284.70 kJ per mol. Conclusion: Bioactive peptide molecule is predicted to be a candidate for HIV1 protease inhibitor. Keywords: AIDS, HIV1 protease, bioactive peptides, protein-peptide docking, in silico

scholarly journals In Silico Bioactive Peptide Prediction from The Enzymatic Hydrolysates of Edible Seaweed Rubisco Large Chain

2021 ◽  
Vol 21 (12) ◽  
pp. 615-625
Author(s):  
Ayse Kose
Keyword(s):  
In Silico ◽  
Bioactive Peptides ◽  
Antioxidant Properties ◽  
In Silico Analysis ◽  
Bioactive Peptide ◽  
Bioactive Substances ◽  
Edible Seaweed ◽  
Ic50 Values ◽  
Peptide Prediction ◽  
Ancient Food

Seaweeds are one of the ancient food supplements on Earth. Especially Asian countries use seaweeds as the fundamental ingredient in their cuisine. Seaweeds are photosynthetic organisms living in aquatic ecosystems and in the coastal territories. Seaweeds out of farm areas are frequently observed as coastal wastes. However, seaweeds are outstanding sources for bioactive substances and investigation bioactive properties of seaweed RuBisCO has never been done. RuBisCO is the most abundant protein on Earth but a vast amount of RuBisCO goes through waste. In this study, bioactive peptide prediction of frequently consumed seaweed RuBisCO proteins were analyzed in silico to identify possible bioactive peptides as substitute or support for grain, meat, and dairy based bioactive peptides. A huge portion of peptides were di-, tri- peptides with IC50 values less than 300 µM according to the comparison of BIOPEP database. Including gastric digestion, more than half of the peptides showed DDP-IV and ACE inhibitory activity followed by antioxidant properties. Also, novel antiinflammatory and anti-cancer peptides were found through in silico analysis.

scholarly journals Mengidentifikasi Peptida Bioaktif Angiotensin Converting Enzyme-inhibitor (ACEi) dari Kasein β Susu Kambing dengan Polimorfismenya Melalui Teknik In Silico

2019 ◽  
Vol 7 (4) ◽  
Author(s):  
Hermawan Setyo Widodo ◽  
Tridjoko Wisnu Murti ◽  
Ali Agus ◽  
Widodo Widodo
Keyword(s):  
Angiotensin Converting Enzyme ◽  
In Silico ◽  
Digestive Enzymes ◽  
Bioactive Peptides ◽  
Enzyme Inhibitor ◽  
Goat Milk ◽  
Bioactive Peptide ◽  
Converting Enzyme ◽  
Lipinski’S Rule ◽  
Lipinski’S Rule Of Five

Susu kambing memiliki komponen protein salah satunya protein β dan secara umum terjadi polimorfisme pada level protein. Perubahan urutan asam amino akibat polimorfisme memungkinkan adanya potensi dihasilkannya peptida bioaktif penghambat enzim pengubah angiotensin (ACEi). Penelitian ini bertujuan untuk menyaring peptida bioaktif yang berpotensi sebagai ACEi dari kasein β kambing beserta polimorfismenya. Penelitian ini dilakukan dengan teknik in silico terhadap sekuen kasein β kambing serta struktur tiga dimensi human testicular ACE. Langkah yang dilakukan dalam penelitian ini meliputi simulasi pemotongan peptida dengan enzim pencernaan (pepsin, tripsin dan kimotripsin), peninjauan karakteristik peptida lalu simulasi docking ligan-reseptor. Tampilan parameter Lipinski’s Rule of Five (Ro5), bioaktivitas dan energi afinitas dipertimbangkan untuk memilih peptida bioaktif. Hasil yang didapat menunjukkan bahwa ditemukan peptida bioaktif yakni INK (Ile-Asp-Lys) yang memiliki kemampuan hampir setara dengan lisinopril (afinitas energi -8,2kkal/mol vs. -8,3kkal/mol). Peptida INK dapat ditemukan dari hasil hidrolisis dari alel A, C, D dan E, sehingga polimorfisme tidak menyebabkan perbedaan produksi peptida bioaktif. Kesimpulan yang dapat diambil yakni kasein β susu kambing jika dicerna dengan enzim pencernaan dapat menghasilkan peptida bioaktif ACEi yakni INK.Identification of Angiotensin Converting Enzyme-inhibitor (ACEi) Bioactive Peptide from Goat Milk β-Casein with It's Polymorphism by In Silico TechniqueAbstractPolymorphism eventually may be occurred at the protein level. Changes in the amino acid sequence due to polymorphism may exhibit a potential action to generate of the angiotensin-converting enzyme inhibitors (ACEi) bioactive peptide. This study is aimed to assess bioactive peptides that have a great potent value as ACEi from goat β casein along with its polymorphism. The research was done by in silico technique on goat β-casein sequence and three-dimensional structure human testicular ACE. Peptide-cutting simulations with digestive enzymes (pepsin, trypsin and chymotrypsin), peptide properties review, then ligand-receptor docking simulations was applied in this research. Appearance of Lipinski's Rule of Five (Ro5), bioactivity and affinity energy were considered for selecting bioactive peptides. The results show that bioactive peptide found as INK (Ile-Asp-Lys) which had similar ability as lisinopril (energy affinity –8.2kcal/mol vs. –8.3kcal/mol). The INK peptides could be found from the hydrolysis resulted in alleles A, C, D and E, therefore polymorphism did not affect the differences of production of bioactive peptides. A conclusion, processed goat milk β casein with digestive enzymes could produce ACEi of INK as bioactive peptide.

In silico analysis of molecular interactions between HIV-1 glycoprotein gp120 and TNF receptors

2021 ◽  
pp. 104837
Author(s):  
Neyla Maria Pereira Alves ◽  
Ronald Rodrigues de Moura ◽  
Lucas Coêlho Bernardo ◽  
Almerinda Agrelli ◽  
Ana Sofia Lima Estevão de Oliveira ◽  
...  
Keyword(s):  
Molecular Interactions ◽  
In Silico ◽  
In Silico Analysis ◽  
Tnf Receptors ◽  
Glycoprotein Gp120 ◽  
Silico Analysis ◽  
Hiv 1

Experimental and ‘in silico’ analysis of the effect of pH on HIV-1 protease inhibitor affinity: Implications for the charge state of the protein ionogenic groups

2012 ◽  
Vol 20 (15) ◽  
pp. 4838-4847 ◽  
Author(s):  
José L. Domínguez ◽  
Thomas Gossas ◽  
M. Carmen Villaverde ◽  
U. Helena Danielson ◽  
Fredy Sussman
Keyword(s):  
Protease Inhibitor ◽  
Charge State ◽  
In Silico ◽  
In Silico Analysis ◽  
Ionogenic Groups ◽  
Effect Of Ph ◽  
Silico Analysis ◽  
Hiv 1

scholarly journals HIV-1 Gag Non-Cleavage Site PI Resistance Mutations Stabilize Protease/Gag Substrate Complexes in Silico via a Substrate-Clamp

BioChem ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 190-209
Author(s):  
Gary S. Laco
Keyword(s):  
Protease Inhibitor ◽  
Active Site ◽  
In Silico ◽  
Cleavage Site ◽  
Cleavage Sites ◽  
Resistance Mutations ◽  
Cleavage Rate ◽  
Protease Inhibitor Resistance ◽  
Inhibitor Resistance ◽  
Hiv 1

HIV-1 protease active site inhibitors are a key part of antiretroviral therapy, though resistance can evolve rendering therapy ineffective. Protease inhibitor resistance typically starts with primary mutations around the active site, which reduces inhibitor binding, protease affinity for substrate cleavage site residues P4-P4′, and viral replication. This is often followed by secondary mutations in the protease substrate-grooves which restore viral replication by increasing protease affinity for cleavage site residues P12-P5/P5′-P12′, while maintaining resistance. However, mutations in Gag alone can also result in resistance. The Gag resistance mutations can occur in cleavage sites (P12-P12′) to increase PR binding, as well as at non-cleavage sites. Here we show in silico that Gag non-cleavage site protease inhibitor resistance mutations can stabilize protease binding to Gag cleavage sites which contain structured subdomains on both sides: SP1/NC, SP2/p6, and MA/CA. The Gag non-cleavage site resistance mutations coordinated a network of H-bond interactions between the adjacent structured subdomains of the Gag substrates to form a substrate-clamp around the protease bound to cleavage site residues P12-P12′. The substrate-clamp likely slows protease disassociation from the substrate, restoring the cleavage rate in the presence of the inhibitor. Native Gag substrates can also form somewhat weaker substrate-clamps. This explains the 350-fold slower cleavage rate for the Gag CA/SP1 cleavage site in that the CA-SP1 substrate lacks structured subdomains on both sides of the cleavage site, and so cannot form a substrate-clamp around the PR.

scholarly journals IN SILICO INVESTIGATION OF ECHINODERMATA SECONDARY METABOLITES AS HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1) REVERSE TRANSCRIPTASE INHIBITORS

2020 ◽  
pp. 51-55
Author(s):  
NURRAHMA NAZWIR ◽  
ARRY YANUAR ◽  
REZI RIADHI SYAHDI
Keyword(s):  
Human Immunodeficiency Virus ◽  
In Silico ◽  
Immune Surveillance ◽  
Hiv Infections ◽  
Literature Searches ◽  
Immunodeficiency Virus ◽  
Recent Trends ◽  
Immunodeficiency Syndrome ◽  
Hiv 1

Objective: Human immunodeficiency virus (HIV) targets the immune system and weakens immune surveillance and defenses against infections,leading to acute immunodeficiency syndrome. Recent trends in drug discovery from natural sources emphasize investigations of compounds frommarine ecosystems.Methods: In this study, we compiled a database of chemical compounds from echinoderms and virtually screened for those that inhibit HIV-1 reversetranscriptase (RT). The database was generated from literature searches. Virtual screening analyses for inhibitors of HIV-1 RT were then performedusing AutoDock software.Results: Based on screening results, the top thirteen ranked compounds were nobilisidenol B, Ech_005, 17-deoxyholothurinogenin,22,25-oxidoholothurinogenin, Ech_022, Ech_026, Ech_021, nobilisidenol A, Ech_025, 5α-cholest-8(14)-ene-3ß,7α-diol, astropecten A, Ech_004, andphrygiasterol.Conclusion: The present in silico screening analyses of compounds from marine ecosystems can be used to identify candidate compounds with highpotential as drugs for the treatment of refractory HIV infections.

scholarly journals Identifikasi Peptida Bioaktif dari Protein Kedelai sebagai Inhibitor Enzim α-glukosidase untuk Kandidat Antidiabetes

2020 ◽  
Vol 17 (2) ◽  
pp. 101-109
Author(s):  
Taufik Muhammad Fakih ◽  
Mentari Luthfika Dewi
Keyword(s):  
Molecular Interactions ◽  
Metabolic Disorders ◽  
Enzyme Inhibitor ◽  
Therapeutic Potential ◽  
Binding Free Energy ◽  
Peptide Sequencing ◽  
Bioactive Peptide ◽  
Suitable Candidate ◽  
Discovery Studio ◽  
Peptide Docking

Diabetes mellitus is one of the endocrine metabolic disorders that has caused morbidity and mortality worldwide. Α-glucosidase inhibitor which plays an important role in carbohydrate metabolism is needed to avoid postprandial hyperglycemia. A bioactive peptide derived from soy protein was chosen as an alternative treatment for diabetes because of its therapeutic potential. Several bioactive peptides have been shown to inhibit the α-glucosidase enzyme, such as the bioactive peptide LLPLPVLK, SWLRL, and WLRL. This study aims to identify and evaluate molecular interactions that occur between bioactive peptide molecules and α-glucosidase enzyme macromolecules using protein-peptide docking methods through in silico. Bioactive peptide sequencing was first modeled using the PEP-FOLD software. The best conformation was chosen for an interaction study of the α-glucosidase enzyme macromolecule using HPEPDock software. Further exploration was carried out on the molecular interactions formed using BIOVIA Discovery Studio 2020 software. Based on the results of molecular docking, the WLRL bioactive peptide has the best affinity against the α-glucosidase enzyme, with a binding free energy value of −748.12 kJ/mol. Therefore, the bioactive peptide is predicted to be a suitable candidate for the α-glucosidase enzyme inhibitor.

Role of 4-O Galloylchlorogenic Acid in Lung Cancer- An Insilico Approach

2017 ◽  
Vol 9 (5) ◽  
Author(s):  
Jaynthy C. ◽  
N. Premjanu ◽  
Abhinav Srivastava
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
In Silico ◽  
Computational Study ◽  
Regulation Mechanism ◽  
Down Regulation ◽  
Fruit Extract ◽  
In Vitro Techniques ◽  
Discovery Studio

Cancer is a major disease with millions of patients diagnosed each year with high mortality around the world. Various studies are still going on to study the further mechanisms and pathways of the cancer cell proliferation. Fucosylation is one of the most important oligosaccharide modifications involved in cancer and inflammation. In cancer development increased core fucosylation by FUT8 play an important role in cell proliferation. Down regulation of FUT8 expression may help cure lung cancer. Therefore the computational study based on the down regulation mechanism of FUT8 was mechanised. Sapota fruit extract, containing 4-Ogalloylchlorogenic acid was used as the inhibitor against FUT-8 as target and docking was performed using in-silico tool, Accelrys Discovery Studio. There were several conformations of the docked result, and conformation 1 showed 80% dock score between the ligand and the target. Further the amino acids of the inhibitor involved in docking were studied using another tool, Ligplot. Thus, in-silico analysis based on drug designing parameters shows that the fruit extract can be studied further using in-vitro techniques to know its pharmacokinetics.

Sign in / Sign up

Export Citation Format

Share Document