A molecular dynamic simulation approach : development of dengue virus vaccine by affinity improvement techniques
This study is about proposing a vaccine for all four strains of dengue virus (DENV) that could be an important approach for reaching the WHO goal of reducing dengue morbidity and mortality. The significance of the DENV envelope proteins III lies in the fact that it elicits an immune response and hence can be a potential vaccine design candidate. This domain appears to play a key role in the host cell receptor binding for viral entry and in inducing long lasting protective immunity against the infection. We used long molecular dynamic simulation and mutagenesis scanning methods to provide the dynamic environment and propose the potential mutation that may result in enhancing the binding specificity and affinity of the antigen-antibody (Ag-Ab) complex. The binding free energetics were also estimated using free energy perturbation method. One charged mutation that is theorinine 93L to arginine interacting with epitopic glutamic acid 368 strongly contributing in increasing the binding affinity as well as specificity, predicted as -9.6 kcal/mol gain in 2H12-Fab with dengue envelope domain III binding free energy relative to the wild-type. In conclusion, the one charged residue that showed theoretically enhances the binding affinity of Ag-Ab complex by making couple of interactions i.e. by substituting theorinine to arginine in the antibody chains and can be considered as potential dengue vaccine candidate.Communicated by Ramaswamy H. Sarma.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
|---|---|
| Enthalten in: |
Journal of biomolecular structure & dynamics - 40(2022), 1 vom: 15. Jan., Seite 61-76 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Rafi, Sidra [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Antibody |
|---|
| Anmerkungen: |
Date Completed 02.02.2022 Date Revised 02.02.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1080/07391102.2020.1811771 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM314382720 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM314382720 | ||
| 003 | DE-627 | ||
| 005 | 20231225152616.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/07391102.2020.1811771 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1047.xml |
| 035 | |a (DE-627)NLM314382720 | ||
| 035 | |a (NLM)32865135 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Rafi, Sidra |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A molecular dynamic simulation approach |b development of dengue virus vaccine by affinity improvement techniques |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 02.02.2022 | ||
| 500 | |a Date Revised 02.02.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a This study is about proposing a vaccine for all four strains of dengue virus (DENV) that could be an important approach for reaching the WHO goal of reducing dengue morbidity and mortality. The significance of the DENV envelope proteins III lies in the fact that it elicits an immune response and hence can be a potential vaccine design candidate. This domain appears to play a key role in the host cell receptor binding for viral entry and in inducing long lasting protective immunity against the infection. We used long molecular dynamic simulation and mutagenesis scanning methods to provide the dynamic environment and propose the potential mutation that may result in enhancing the binding specificity and affinity of the antigen-antibody (Ag-Ab) complex. The binding free energetics were also estimated using free energy perturbation method. One charged mutation that is theorinine 93L to arginine interacting with epitopic glutamic acid 368 strongly contributing in increasing the binding affinity as well as specificity, predicted as -9.6 kcal/mol gain in 2H12-Fab with dengue envelope domain III binding free energy relative to the wild-type. In conclusion, the one charged residue that showed theoretically enhances the binding affinity of Ag-Ab complex by making couple of interactions i.e. by substituting theorinine to arginine in the antibody chains and can be considered as potential dengue vaccine candidate.Communicated by Ramaswamy H. Sarma | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Dengue | |
| 650 | 4 | |a antibody | |
| 650 | 4 | |a free energy perturbation | |
| 650 | 4 | |a molecular dynamic simulation | |
| 650 | 4 | |a mutation | |
| 650 | 4 | |a vaccine | |
| 650 | 7 | |a Dengue Vaccines |2 NLM | |
| 650 | 7 | |a Vaccines |2 NLM | |
| 650 | 7 | |a Viral Envelope Proteins |2 NLM | |
| 700 | 1 | |a Yasmin, Sabina |e verfasserin |4 aut | |
| 700 | 1 | |a Uddin, Reaz |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of biomolecular structure & dynamics |d 1985 |g 40(2022), 1 vom: 15. Jan., Seite 61-76 |w (DE-627)NLM012639974 |x 1538-0254 |7 nnns |
| 773 | 1 | 8 | |g volume:40 |g year:2022 |g number:1 |g day:15 |g month:01 |g pages:61-76 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/07391102.2020.1811771 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 40 |j 2022 |e 1 |b 15 |c 01 |h 61-76 | ||