designing therapeutic peptides and proteins using open source software
DESCRIPTION
Designing therapeutic peptides and proteins using Open source Software. Dr G P S Raghava, Head Bioinformatics Centre. Institute of Microbial Technology, Chandigarh, India. Email: [email protected] http://crdd.osdd.net/ http://ww.imtech.res.in/raghava/. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/1.jpg)
Institute of Microbial Technology, Chandigarh, India
Email: [email protected] http://crdd.osdd.net/
http://ww.imtech.res.in/raghava/
Email: [email protected] http://crdd.osdd.net/
http://ww.imtech.res.in/raghava/
![Page 2: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/2.jpg)
Peptide/ Proteins
Drug/inhibitor/vaccine/ Disease Diagnostics
Peptide Structure, docked structure
Peptide-Protein Interaction
Adaptive Immunity: B-cell, T-cell Epitope
Innate Immunity: Toll-like receptors
Anti-(bacterial , microbial, cancer, viral) peptides
Mimotopes for diseases diagnostics
Structure prediction: Natural, non-natural , modified bonds
Structure determination: Natural, non-natural , modified bonds
Synthesis: Phase display, SPSS, Codon Suffeling
Natural bioactive peptides from metagenomics
Mimotopes for B/T epitopes Mimicking of Drug Molecules
ADMET: Proteolytic enzymes, Half-life
Oral Delivery : Trans. & Adjuvant
Size Optimization for function/Str.
![Page 3: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/3.jpg)
Application of peptides in treating cancer
Limitation of Peptides & Challenge for Bioinformaticians
Peptide Web Servers
Peptide Databases
Therapeutic Application of Peptides
![Page 4: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/4.jpg)
Therapeutic Application of Biomolecules
Peptide based Drugs (Small Molecule, Peptide, Protein)
• Anticancer peptides• Antibacterial peptides
Peptide for delivering drug • Cell-penetrating peptides• Tumor-homing peptides
Peptide as disease diagnostics• Disease specific Mimotopes
Epitope/Peptide based Vaccines• T-cell epitopes• B-cell epitopes
![Page 5: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/5.jpg)
Limitation of Peptides & Challenges for Bioinformaticians
1. Peptide Degradation (short half-life)
• Large peptide degrading enzymes
• Hepatic/renal Clearance (liver/kidenys)
2. Low Oral Bioavailability (injection)
3. High conformational flexibility
• Environment dependent tertiary structure
• Low selectivity
4. Immunogenicity and antigenicity
5. High cost of production & Storage
• Modification/glycosylation of peptides
![Page 6: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/6.jpg)
Important Resources/Databases
MHCBN: MHC binding and non-binding peptides
CPPsite: Cell penetrating peptides
BCIpep: B-cell epitope datbase
HMRbase: A database of hormones and their receptors
TumorHope: Tumor hoping peptides
TumorHPD: Designing of Tumor Homing Peptides
CellPPD: Designing of cell penetrating peptides
Pepstr: Prediction of Peptide structure
AntiCP: Prediction and designing of anticancer peptides
![Page 7: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/7.jpg)
Pathogens/Invaders
Disease Causing Agents
Innate Immunity Vaccine Delivery
Protective AntigensAdaptive Immunity
Bioinformatics CentreIMTECH, Chandigarh
![Page 8: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/8.jpg)
Innate Immunity Vaccine Delivery
Protective AntigensAdaptive Immunity
Bioinformatics CentreIMTECH, Chandigarh
WHOLEORGANISM
Attenuated
Epitopes (Subunit Vaccine)
Purified Antigen
T cell epitope
![Page 9: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/9.jpg)
Prediction of CTL Epitopes (Cell-mediated immunity)
ER
TAP
Innate Immunity Vaccine Delivery
Protective AntigensAdaptive Immunity
Bioinformatics CentreIMTECH, Chandigarh
![Page 10: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/10.jpg)
Prediction of B-Cell Epitopes
• BCEpred: Prediction of Continuous B-cell epitopes– Benchmarking of existing methods – Poor performance slightly better than random– Combine all properties and achieve accuracy around 58%– Saha and Raghava (2004) ICARIS 197-204.
• ABCpred: ANN based method for B-cell epitope prediction– Extract all epitopes from BCIPEP (around 2400)– 700 non-redundant epitopes used for testing and training– Recurrent neural network– Accuracy 66% achieved– Saha and Raghava (2006) Proteins,65:40-48
• ALGpred: Mapping and Prediction of Allergenic Epitopes– Allergenic proteins– IgE epitope and mapping– Saha and Raghava (2006) Nucleic Acids Research 34:W202-W209
• CBTOPE: Prediction of conformational epitopes
Innate Immunity Vaccine Delivery
Protective AntigensAdaptive Immunity
Bioinformatics CentreIMTECH, Chandigarh
![Page 11: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/11.jpg)
Modelling of Immune System for Designing Epitope-based Vaccines
Adaptive Immunity (Cellular Response) : Thelper Epitopes
Adaptive Immunity (Cellular Response) : CTL Epitopes
Adaptive Immunity (Humoral Response) :B-cell Epitopes
Innate Immunity : Pathogen Recognizing Receptors and ligands
Signal transduction in Immune System
Propred: for promiscuous MHC II binders
MMBpred:for high affinity mutated binders
MHC2pred: SVM based method
MHCBN: A database of MHC/TAP binders and non-binders
Pcleavage: for proteome cleavage sites
TAPpred: for predicting TAP binders
Propred1: for promiscuous MHC I binders
CTLpred: Prediction of CTL epitopes
Cytopred: for classification of Cytokines
BCIpep: A database of B-cell eptioes; ABCpred: for predicting B-cell epitopesALGpred: for allergens and IgE eptopes
HaptenDB: A datbase of haptens
PRRDB: A database of PRRs & ligands
Antibp: for anti-bacterial peptides
![Page 12: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/12.jpg)
Peptide structure prediction
• 3D structures of 77 biologically active peptides (9-20 residues)• 3D structures of 77 biologically active peptides (9-20 residues)
![Page 13: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/13.jpg)
Peptide structure prediction
Averaged backbone root mean deviation before and after energy minimization and dynamics simulations.Averaged backbone root mean deviation before and after energy minimization and dynamics simulations.
![Page 14: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/14.jpg)
Peptide Web Servers
![Page 15: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/15.jpg)
Peptide Web Servers
![Page 16: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/16.jpg)
Designing of antibacterial stable peptides
Scanning of peptides in a protein
Submition of multiple peptides
![Page 17: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/17.jpg)
Peptide Resources/Databases
![Page 18: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/18.jpg)
Peptide Web Servers
![Page 19: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/19.jpg)
Designing of therapeutic peptides against cancer
Anticancer peptides Designing of
effective anticancer peptides
Peptide inhibitors Identification of inhibitors against cancer targets
Cell Penetrating Peptides
CPPsite: Database
CellPred: Design
? Tumor Homing Peptides TumorHoPe: Database TumorHPD:
Design
Peptides Half-life
HLP: prediction in intestine
Depend on environment
Toxicity of Peptides
Immuno-, cyto-toxicity
Off targets
![Page 20: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/20.jpg)
![Page 21: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/21.jpg)
Peptide Resources/Databases
![Page 22: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/22.jpg)
![Page 23: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/23.jpg)
![Page 24: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/24.jpg)
Peptide Resources/Databases
Work in Progress
1. Prediction of CPP 2. Designing CPP 3. Scanning in proteins
![Page 25: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/25.jpg)
![Page 26: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/26.jpg)
![Page 27: Designing therapeutic peptides and proteins using Open source Software](https://reader035.vdocuments.mx/reader035/viewer/2022062309/568146fd550346895db438f5/html5/thumbnails/27.jpg)
Thankyou