Dataset Information

In silico prediction of T- and B-cell epitopes in PmpD: First step towards to the design of a Chlamydia trachomatis vaccine.

ABSTRACT: BACKGROUND:Chlamydia trachomatis is the most common sexually transmitted bacterial infection globally. Currently, there are no vaccines available despite the efforts made to develop a protective one. Polymorphic membrane protein D (PmpD) is an attractive immunogen candidate as it is conserved among strains and it is target of neutralizing antibodies. However, its high molecular weight and its complex structure make it difficult to handle by recombinant DNA techniques. Our aim is to predict B-cell and T-cell epitopes of PmpD. METHOD:A sequence (Genbank AAK69391.2) having 99-100% identity with various serovars of C. trachomatis was used for predictions. NetMHC and NetMHCII were used for T-cell epitope linked to MHC I or MHC II alleles prediction, respectively. BepiPred predicted linear B-cell epitopes. For three dimensional epitopes, PmpD was homology-modeled by Raptor X. Surface epitopes were predicted on its globular structure using DiscoTope. RESULTS:NetMHC predicted 271 T-cell epitopes of 9-12aa with weak affinity, and 70 with strong affinity to MHC I molecules. NetMHCII predicted 2903 T-cell epitopes of 15aa with weak affinity, and 742 with strong affinity to MHC II molecules. Twenty four linear B-cell epitopes were predicted. Raptor X was able to model 91% of the three-dimensional structure whereas 57 residues of discontinuous epitopes were suggested by DiscoTope. Six regions containing B-cell and T-cell epitopes were identified by at least two predictors. CONCLUSIONS:PmpD has potential B-cell and T-cell epitopes distributed throughout the sequence. Thus, several fragments were identified as valuable candidates for subunit vaccines against C. trachomatis.

SUBMITTER: Russi RC

PROVIDER: S-EPMC6138762 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

In silico prediction of T- and B-cell epitopes in PmpD: First step towards to the design of a Chlamydia trachomatis vaccine.

Russi Romina Cecilia RC Bourdin Elian E García María Inés MI Veaute Carolina Melania I CMI

Biomedical journal 20180401 2

<h4>Background</h4>Chlamydia trachomatis is the most common sexually transmitted bacterial infection globally. Currently, there are no vaccines available despite the efforts made to develop a protective one. Polymorphic membrane protein D (PmpD) is an attractive immunogen candidate as it is conserved among strains and it is target of neutralizing antibodies. However, its high molecular weight and its complex structure make it difficult to handle by recombinant DNA techniques. Our aim is to predi ...[more]

PMID: 29866599

Similar Datasets

Project description:Angiotensin II type 1 receptor (AT1R) blockers (ARBs) are among the most prescribed drugs. However, ARB effectiveness varies widely, which may be due to non-synonymous single nucleotide polymorphisms (nsSNPs) within the AT1R gene. The AT1R coding sequence contains over 100 nsSNPs; therefore, this study embarked on determining which nsSNPs may abrogate the binding of selective ARBs. The crystal structure of olmesartan-bound human AT1R (PDB:4ZUD) served as a template to create an inactive apo-AT1R via molecular dynamics simulation (n = 3). All simulations resulted in a water accessible ligand-binding pocket that lacked sodium ions. The model remained inactive displaying little movement in the receptor core; however, helix 8 showed considerable flexibility. A single frame representing the average stable AT1R was used as a template to dock Olmesartan via AutoDock 4.2, MOE, and AutoDock Vina to obtain predicted binding poses and mean Boltzmann weighted average affinity. The docking results did not match the known pose and affinity of Olmesartan. Thus, an optimization protocol was initiated using AutoDock 4.2 that provided more accurate poses and affinity for Olmesartan (n = 6). Atomic models of 103 of the known human AT1R polymorphisms were constructed using the molecular dynamics equilibrated apo-AT1R. Each of the eight ARBs was then docked, using ARB-optimized parameters, to each polymorphic AT1R (n = 6). Although each nsSNP has a negligible effect on the global AT1R structure, most nsSNPs drastically alter a sub-set of ARBs affinity to the AT1R. Alterations within N298 -L314 strongly effected predicted ARB affinity, which aligns with early mutagenesis studies. The current study demonstrates the potential of utilizing in silico approaches towards personalized ARB therapy. The results presented here will guide further biochemical studies and refinement of the model to increase the accuracy of the prediction of ARB resistance in order to increase overall ARB effectiveness.

Project description:A cluster of promising epitopes for the development of human immunodeficiency virus (HIV) vaccines is located in the membrane-proximal external region (MPER) of the gp41 subunit of the HIV envelope spike structure. The crystal structure of the peptide corresponding to the so-called ELDKWA epitope (HIV-1 HxB2 gp41 residues 662-668), in complex with the corresponding broadly neutralizing human monoclonal antibody 2F5, provides a target for structure-based vaccine design strategies aimed at finding macromolecular carriers that are able to present this MPER-derived epitope with optimal antigenic activity. To this end, a series of replica exchange molecular dynamics computer simulations was conducted to characterize the distributions of conformations of ELDKWA-based epitopes inserted into a rhinovirus carrier and to identify those with the highest fraction of conformations that are able to bind 2F5. The length, hydrophobic character, and precise site of insertion were found to be critical for achieving structural similarity to the target crystal structure. A construct with a high degree of complementarity to the corresponding determinant region of 2F5 was obtained. This construct was employed to build a high-resolution structural model of the complex between the 2F5 antibody and the chimeric human rhinovirus type 14:HIV-1 ELDKWA virus particle. Additional simulations, which were conducted to study the conformational propensities of the ELDKWA region in solution, confirm the hypothesis that the ELDKWA region of gp41 is highly flexible and capable of assuming helical conformations (as in the postfusion helical bundle structure) and beta-turn conformations (as in the complex with the 2F5 antibody). These results also suggest that the ELDKWA epitope can be involved in intramolecular--and likely intermolecular--hydrophobic interactions. This tendency offers an explanation for the observation that mutations decreasing the hydrophobic character of the MPER in many cases result in conformational changes that increase the affinity of this region for the 2F5 antibody.

Dataset Information

In silico prediction of T- and B-cell epitopes in PmpD: First step towards to the design of a Chlamydia trachomatis vaccine.

Publications

In silico prediction of T- and B-cell epitopes in PmpD: First step towards to the design of a Chlamydia trachomatis vaccine.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure