Subangstrom Accuracy in pHLA-I Modeling by Rosetta FlexPepDock Refinement Protocol

Liu, Tengfei; Pan, Xianchao; Li, Chao; Tan, Wen; Qu, Sujun; Li, Yang; Wang, Bochu; Hu, Mingming

doi:10.1021/ci500393h

Cited by 34 publications

(27 citation statements)

References 33 publications

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“…Increasing flexibility is captured by the change in color gradient from blue to white to red. ( C ) HLA-E*01:03 binding profile obtained from a ROSETTA-based docking approach (30) of 11 optimal, MHC-E-restricted, SIVgag epitopic peptides. The backbones of these peptides adopt a similar conformation as shown with multiple colors in front of the binding groove cross-section.…”

Section: Figmentioning

confidence: 99%

Broadly targeted CD8 ⁺ T cell responses restricted by major histocompatibility complex E

Hansen

Burwitz

et al. 2016

Science

270

431

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Major histocompatibility complex (MHC)-E is a highly conserved, ubiquitously expressed, non-classical MHC-Ib molecule with limited polymorphism primarily involved in NK cell regulation. We found that vaccination of rhesus macaques (RM) with ΔRh157.5/.4 Rhesus Cytomegalovirus (RhCMV) vectors results in MHC-E-restricted presentation of highly varied peptide epitopes to CD8α/β+ T cells, approximately 4 distinct epitopes per 100 amino acids in all tested antigens. Computational structural analysis revealed that MHC-E provides heterogeneous chemical environments for diverse side chain interactions within a stable, open binding groove. Since MHC-E is up-regulated on cells infected with HIV/SIV and other persistent viruses to evade NK cell activity, MHC-E-restricted CD8+ T cell responses have the potential to exploit pathogen immune evasion adaptations, a capability that might endow these unconventional responses with superior efficacy.

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Section: Figmentioning

confidence: 99%

Broadly targeted CD8 ⁺ T cell responses restricted by major histocompatibility complex E

Hansen

Burwitz

et al. 2016

Science

270

431

View full text Add to dashboard Cite

show abstract

“…The MHC class I ad class II molecules were downloaded from RCSB PDB database (https://www.rcsb.org/). Those that were not available were in PDB database were retrieved from pHLA database (https://www.phla3d.com.br/) [42]. The structures of the SARS-CoV-2 proteins were constructed using I-TASSER (https://zhanglab.ccmb.med.umich.edu/I-TASSER/) [43]and HTL and CTL epitopes were mapped and their structures were retrieved using PyMol tool.…”

Section: Molecular Interaction Of the Hla-epitope Pairmentioning

confidence: 99%

Scrutinizing the SARS-CoV-2 protein information for the designing an effective vaccine encompassing both the T-cell and B-cell epitopes

Jain

Shankar

Majee

et al. 2020

Preprint

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Novel SARS coronavirus (SARS-CoV-2) has caused a pandemic condition world-wide and has been declared as public health emergency of International concern by WHO in a very short span of time. The community transmission of this highly infectious virus has severely affected various parts of China, Italy, Spain and USA among others. The prophylactic solution against SARS-CoV-2 infection is challenging due to the high mutation rate of its RNA genome. Herein, we exploited a next generation vaccinology approach to construct a multi-epitope vaccine candidate against SARS-CoV-2 with high antigenicity, safety and efficacy to combat this deadly infectious agent. The whole proteome was scrutinized for the screening of highly conserved, antigenic, non-allergen and non-toxic epitopes having high population coverage that can elicit both humoral and cellular mediated immune response against COVID-19 infection. These epitopes along with four different adjuvants were utilized to construct a multi-epitope vaccine candidate that can generate strong immunological memory response having high efficacy in humans. Various physiochemical analyses revealed the formation of a stable vaccine product having a high propensity to form a protective solution against the detrimental SARS-CoV-2 strain with high efficacy. The vaccine candidate interacted with immunological receptor TLR3 with high affinity depicting the generation of innate immunity. Further, the codon optimization and in silico expression show the plausibility of the high expression and easy purification of the vaccine product. Thus, this present study provides an initial platform of the rapid generation of an efficacious protective vaccine for combating COVID-19.

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“…Rosetta FlexPepDock is a well benchmarked and widely used tool for the high-resolution refinement of peptide-protein complexes [23,44]. As demonstrated in several studies, it enables obtaining sub-Angstrom quality of protein-peptide structures [22,44,45]. The initial structure FlexPepDock refinement consists of several operational modes that may be freely combined according to a specific task or input quality.…”

Section: Stage 3: Structure Refinement Using Rosetta Flexpepdockmentioning

confidence: 99%

Docking of peptides to GPCRs using a combination of CABS-dock with FlexPepDock refinement

Badaczewska-Dawid

Kmiecik

Koliński

2020

Preprint

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The structural description of peptide ligands bound to G protein-coupled receptors (GPCRs) is important for the discovery of new drugs and deeper understanding of the molecular mechanisms of life. Here we describe a three-stage protocol for the molecular docking of peptides to GPCRs using a set of different programs: (1) CABS-dock for docking fully flexible peptides; (2) PD2 method for the reconstruction of atomistic structures from C-alpha traces provided by CABS-dock and (3) Rosetta FlexPepDock for the refinement of protein-peptide complex structures and model scoring. We evaluated the proposed protocol on the set of 7 different GPCR-peptide complexes (including one containing a cyclic peptide) for which crystallographic structures are available. We show that CABS-dock produces high resolution models in the sets of top-scored models. These sets of models, after reconstruction to all-atom representation, can be further improved by Rosetta high-resolution refinement and/or minimization, leading in most of the cases to sub-Angstrom accuracy in terms of interface RMSD measure.

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Subangstrom Accuracy in pHLA-I Modeling by Rosetta FlexPepDock Refinement Protocol

Cited by 34 publications

References 33 publications

Broadly targeted CD8 ⁺ T cell responses restricted by major histocompatibility complex E

Broadly targeted CD8 ⁺ T cell responses restricted by major histocompatibility complex E

Scrutinizing the SARS-CoV-2 protein information for the designing an effective vaccine encompassing both the T-cell and B-cell epitopes

Docking of peptides to GPCRs using a combination of CABS-dock with FlexPepDock refinement

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Subangstrom Accuracy in pHLA-I Modeling by Rosetta FlexPepDock Refinement Protocol

Cited by 34 publications

References 33 publications

Broadly targeted CD8 + T cell responses restricted by major histocompatibility complex E

Broadly targeted CD8 + T cell responses restricted by major histocompatibility complex E

Scrutinizing the SARS-CoV-2 protein information for the designing an effective vaccine encompassing both the T-cell and B-cell epitopes

Docking of peptides to GPCRs using a combination of CABS-dock with FlexPepDock refinement

Contact Info

Product

Resources

About

Broadly targeted CD8 ⁺ T cell responses restricted by major histocompatibility complex E

Broadly targeted CD8 ⁺ T cell responses restricted by major histocompatibility complex E