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Assessing Peptide Binding to MHC II: An Accurate Semiempirical Quantum Mechanics Based Proposal

Ortiz Mahecha, Carlos A.; Bohórquez, Hugo Javier; Agudelo, William A.; Patarroyo, Manuel A.; Patarroyo, Manuel Elkin; Suárez, Carlos F. (2019)

Estimating peptide-major histocompatibility complex (pMHC) binding using structural computational methods has an impact on understanding overall immune function triggering adaptive immune responses in MHC class II molecules. ...
Babesia Bovis Ligand-Receptor Interaction: AMA-1 Contains Small Regions Governing Bovine Erythrocyte Binding

Cuy-Chaparro, Laura; Bohórquez, Michel David; Arevalo-Pinzon, Gabriela; Castañeda-Ramírez, Jeimmy Johana; Suárez, Carlos F. (2021)

Apical membrane antigen 1 is a microneme protein which plays an indispensable role during Apicomplexa parasite invasion. The detailed mechanism of AMA-1 molecular interaction with its receptor on bovine erythrocytes has ...
Erratum: Publisher Correction: Mass & secondary structure propensity of amino acids explain their mutability and evolutionary replacements

Bohórquez, Hugo J.; Suárez, Carlos F.; Patarroyo, Manuel Elkin (2018)

Why is an amino acid replacement in a protein accepted during evolution? The answer given by bioinformatics relies on the frequency of change of each amino acid by another one and the propensity of each to remain unchanged. ...
Major Histocompatibility Complex Class II (DRB3) Genetic Diversity in Spanish Morucha and Colombian Normande Cattle Compared to Taurine and Zebu Populations

Bohórquez, Michel David; Ordoñez, Diego; Suárez, Carlos F.; Vicente, Belén; López Abán, Julio; Muro, Antonio; Ordóñez, Iván; Patarroyo, Manuel A. (2020)

Bovine leukocyte antigens (BoLA) have been used as disease markers and immunological traits in cattle due to their primary role in pathogen recognition by the immune system. A higher MHC allele diversity in a population ...
Malaria: Paving the way to developing peptide-based vaccines against invasion in infectious diseases

Reyes, César; Molina Franky, Jessica S.; Aza Conde, Jorge; Suárez, Carlos F.; Pabón, Laura; Moreno Vranich, Armando; Patarroyo, Manuel A.; Patarroyo, Manuel Elkin (2020)

Malaria remains a large-scale public health problem, killing more than 400,000 people and infecting up to 230 million worldwide, every year. Unfortunately, despite numerous efforts and research concerning vaccine development, ...
Mass & secondary structure propensity of amino acids explain their mutability and evolutionary replacements

Bohórquez, Hugo J.; Suárez, Carlos F.; Patarroyo, Manuel Elkin (2017)

Why is an amino acid replacement in a protein accepted during evolution? The answer given by bioinformatics relies on the frequency of change of each amino acid by another one and the propensity of each to remain unchanged. ...
Plasmodium vivax Pv12 B-cell epitopes and HLA-DRβ1-dependent T-cell epitopes in vitro antigenicity

Yepes Pérez, Yoelis; López, Carolina; Suárez, Carlos F.; Patarroyo, Manuel A. (2018)

Malaria is an infectious disease caused by parasites from the genus Plasmodium (P. falciparum and P. vivax are responsible for 90% of all clinical cases); it is widely distributed throughout the world’s tropical and ...
Semi-empirical quantum evaluation of peptide – MHC class II binding

González, Ronald; Suárez, Carlos F.; Bohórquez, Hugo J.; Patarroyo, Manuel A.; Patarroyo, Manuel E. (2017)

Peptide presentation by the major histocompatibility complex (MHC) is a key process for triggering a specific immune response. Studying peptide-MHC (pMHC) binding from a structural-based approach has potential for reducing ...
Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans

Suárez, Carlos F.; Pabón, Laura; Barrera, Ana; Aza Conde, Jorge; Patarroyo, Manuel Alfonso; Patarroyo, Manuel Elkin (2017)

More than 50 years ago the owl monkey (genusAotus) was found to be highly susceptible to developinghuman malaria, making it an excellent experimental model for this disease. Microbes and parasites'(especially malaria) ...

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Assessing Peptide Binding to MHC II: An Accurate Semiempirical Quantum Mechanics Based Proposal
...
Ortiz Mahecha, Carlos A. | 2019

Estimating peptide-major histocompatibility complex (pMHC) binding using structural computational methods has an impact on understanding overall immune function triggering adaptive immune responses in MHC class II molecules. We developed a strategy for optimizing pMHC structure interacting with water molecules and for calculating the binding energy of receptor + ligand systems, such as HLA-DR1 + HA, HLA-DR1 + CLIP, HLA-DR2 + MBP, and HLA-DR3 + CLIP, as well as a monosubstitution panel. Taking pMHC's structural properties, we assumed that ΔH ≫ -TΔS would generate a linear model for estimating relative free energy change, using three semiempirical quantum methods (PM6, PM7, and FMO-SCC-DFTB3) along with the implicit solvent models, and considering proteins in neutral and charged states. Likewise, we confirmed our approach's effectiveness in calculating binding energies having high correlation with experimental data and low root-mean-square error (<2 kcal/mol). All in all, our pipeline differentiates weak from strong peptide binders as a reliable method for studying pMHC interactions.

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Babesia Bovis Ligand-Receptor Interaction: AMA-1 Contains Small Regions Governing Bovine Erythrocyte Binding
...
Cuy-Chaparro, Laura | 2021

Apical membrane antigen 1 is a microneme protein which plays an indispensable role during Apicomplexa parasite invasion. The detailed mechanism of AMA-1 molecular interaction with its receptor on bovine erythrocytes has not been completely defined in Babesia bovis. This study was focused on identifying the minimum B. bovis AMA-1-derived regions governing specific and high-affinity binding to its target cells. Different approaches were used for detecting ama-1 locus genetic variability and natural selection signatures. The binding properties of twelve highly conserved 20-residue-long peptides were evaluated using a sensitive and specific binding assay based on radio-iodination. B. bovis AMA-1 ectodomain structure was modelled and refined using molecular modelling software. NetMHCIIpan software was used for calculating B-and T-cell epitopes. The B. bovis ama-1 gene had regions under functional constraint, having the highest negative selective pressure intensity in the Domain I encoding region. Interestingly, B. bovis AMA-1-DI (100YMQKFDIPRNHGSGIYVDLG119 and120GYESVGSKSYRMPVGKCPVV139 ) and DII (302CPMHPVRDAIFGKWSGGSCV321 )-derived peptides had high specificity interaction with erythrocytes and bound to a chymotrypsin and neuraminidase-treatment sensitive receptor. DI-derived peptides appear to be exposed on the protein’s surface and contain predicted B-and T-cell epitopes. These findings provide data (for the first-time) concerning B. bovis AMA-1 functional subunits which are important for establishing receptor-ligand interactions which could be used in synthetic vaccine development.

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Erratum: Publisher Correction: Mass & secondary structure propensity of amino acids explain their mutability and evolutionary replacements
...
Bohórquez, Hugo J. | 2018

Why is an amino acid replacement in a protein accepted during evolution? The answer given by bioinformatics relies on the frequency of change of each amino acid by another one and the propensity of each to remain unchanged. We propose that these replacement rules are recoverable from the secondary structural trends of amino acids. A distance measure between high-resolution Ramachandran distributions reveals that structurally similar residues coincide with those found in substitution matrices such as BLOSUM: Asn ↔ Asp, Phe ↔ Tyr, Lys ↔ Arg, Gln ↔ Glu, Ile ↔ Val, Met → Leu; with Ala, Cys, His, Gly, Ser, Pro, and Thr, as structurally idiosyncratic residues. We also found a high average correlation (R¯¯¯¯ = 0.85) between thirty amino acid mutability scales and the mutational inertia (I X ), which measures the energetic cost weighted by the number of observations at the most probable amino acid conformation. These results indicate that amino acid substitutions follow two optimally-efficient principles: (a) amino acids interchangeability privileges their secondary structural similarity, and (b) the amino acid mutability depends directly on its biosynthetic energy cost, and inversely with its frequency. These two principles are the underlying rules governing the observed amino acid substitutions.

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Major Histocompatibility Complex Class II (DRB3) Genetic Diversity in Spanish Morucha and Colombian Normande Cattle Compared to Taurine and Zebu Populations
...
Bohórquez, Michel David | 2020

Bovine leukocyte antigens (BoLA) have been used as disease markers and immunological traits in cattle due to their primary role in pathogen recognition by the immune system. A higher MHC allele diversity in a population will allow presenting a broader peptide repertoire. However, loss of overall diversity due to domestication process can decrease a population’s peptide repertoire. Within the context of zebu and taurine cattle populations, BoLA-DRB3 genetic diversity in Spanish Morucha and Colombian Normande cattle was analyzed and an approach to estimate functional diversity was performed. Sequence-based typing was used for identifying 29, 23, 27, and 28 alleles in Spanish Morucha, Nariño-, Boyacá-, and Cundinamarca-Normande cattle, respectively. These breeds had remarkably low heterozygosity levels and the Hardy-Weinberg principle revealed significant heterozygote deficiency. FST and DA genetic distance showed that Colombian Normande populations had greater variability than other phenotypically homogeneous breeds, such as Holstein. It was also found that Spanish Morucha cattle were strongly differentiated from other cattle breeds. Spanish Morucha had greater divergence in the peptide-binding region regarding other cattle breeds. However, peptide-binding region covariation indicated that the potential peptide repertoire seemed equivalent among cattle breeds. Despite the genetic divergence observed, the extent of the potential peptide repertoire in the cattle populations studied appears to be similar and thus their pathogen recognition potential should be equivalent, suggesting that functional diversity might persist in the face of bottlenecks imposed by domestication and breeding.

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Malaria: Paving the way to developing peptide-based vaccines against invasion in infectious diseases
...
Reyes, César | 2020

Malaria remains a large-scale public health problem, killing more than 400,000 people and infecting up to 230 million worldwide, every year. Unfortunately, despite numerous efforts and research concerning vaccine development, results to date have been low and/or strain-specific. This work describes a strategy involving Plasmodium falciparum Duffy binding-like (DBL) and reticulocyte-binding protein homologue (RH) family-derived minimum functional peptides, netMHCIIpan3.2 parental and modified peptides’ in silico binding prediction and modeling some Aotus major histocompatibility class II (MHCII) molecules based on known human molecules’ structure to understand their differences. These are used to explain peptides’ immunological behaviour when used as vaccine components in the Aotus model. Despite the great similarity between human and Aotus immune system molecules, around 50% of Aotus allele molecules lack a counterpart in the human immune system which could lead to an Aotus-specific vaccine. It was also confirmed that functional Plasmodium falciparum’ conserved proteins are immunologically silent (in both the animal model and in-silico prediction); they must therefore be modified to elicit an appropriate immune response. Some peptides studied here had the desired behaviour and can thus be considered components of a fully-protective antimalarial vaccine.

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Mass & secondary structure propensity of amino acids explain their mutability and evolutionary replacements
...
Bohórquez, Hugo J. | 2017

Why is an amino acid replacement in a protein accepted during evolution? The answer given by bioinformatics relies on the frequency of change of each amino acid by another one and the propensity of each to remain unchanged. We propose that these replacement rules are recoverable from the secondary structural trends of amino acids. A distance measure between high-resolution Ramachandran distributions reveals that structurally similar residues coincide with those found in substitution matrices such as BLOSUM: Asn Asp, Phe Tyr, Lys Arg, Gln Glu, Ile Val, Met → Leu; with Ala, Cys, His, Gly, Ser, Pro, and Thr, as structurally idiosyncratic residues. We also found a high average correlation (\overline{R} R = 0.85) between thirty amino acid mutability scales and the mutational inertia (I X ), which measures the energetic cost weighted by the number of observations at the most probable amino acid conformation. These results indicate that amino acid substitutions follow two optimally-efficient principles: (a) amino acids interchangeability privileges their secondary structural similarity, and (b) the amino acid mutability depends directly on its biosynthetic energy cost, and inversely with its frequency. These two principles are the underlying rules governing the observed amino acid substitutions. © 2017 The Author(s).

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Plasmodium vivax Pv12 B-cell epitopes and HLA-DRβ1-dependent T-cell epitopes in vitro antigenicity
...
Yepes Pérez, Yoelis | 2018

Malaria is an infectious disease caused by parasites from the genus Plasmodium (P. falciparum and P. vivax are responsible for 90% of all clinical cases); it is widely distributed throughout the world’s tropical and subtropical regions. The P. vivax Pv12 protein is involved in invasion, is expressed on merozoite surface and has been recognised by antibodies from individuals exposed to the disease. In this study, B- and T-cell epitopes from Pv12 were predicted and characterised to advance in the design of a peptide-based vaccine against malaria. For evaluating the humoral response of individuals exposed to natural P. vivax infection from two endemic areas in Colombia, BepiPred-1.0 software was used for selecting B-cell epitopes. B-cell epitope 39038 displayed the greatest recognition by naturally-acquired antibodies and induced an IgG2/IgG4 response. NetMHCIIpan-3.1 prediction software was used for selecting peptides having high affinity binding for HLA-DRβ1* allele lineages and this was confirmed by in-vitro binding assays. T-epitopes 39113 and 39117 triggered a memory T-cell response (Stimulation Index2) and significant cytokine production. Combining in-silico, in-vitro and functional assays, two Pv12 protein regions (containing peptides 39038, 39040, 39113 and 39117) have thus been characterised as promising vaccine candidates against P. vivax malaria.

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Semi-empirical quantum evaluation of peptide – MHC class II binding
...
González, Ronald | 2017

Peptide presentation by the major histocompatibility complex (MHC) is a key process for triggering a specific immune response. Studying peptide-MHC (pMHC) binding from a structural-based approach has potential for reducing the costs of investigation into vaccine development. This study involved using two semi-empirical quantum chemistry methods (PM7 and FMO-DFTB) for computing the binding energies of peptides bonded to HLA-DR1 and HLA-DR2. We found that key stabilising water molecules involved in the peptide binding mechanism were required for finding high correlation with IC50 experimental values. Our proposal is computationally non-intensive, and is a reliable alternative for studying pMHC binding interactions.

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Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans
...
Suárez, Carlos F. | 2017

More than 50 years ago the owl monkey (genusAotus) was found to be highly susceptible to developinghuman malaria, making it an excellent experimental model for this disease. Microbes and parasites'(especially malaria) tremendous genetic variability became resolved during our malaria vaccine devel-opment, involving conserved peptides having high host cell binding activity (cHABPs); however, cHABPsare immunologically silent and must be specially modified (mHABPs) to induce a perfectfit into majorhistocompatibility complex (MHC) molecules (HLA in humans). Since malarial immunity is mainlyantibody-mediated and controlled by the HLA-DRB genetic region, ~1000Aotushave been molecularlycharacterised for MHC-DRB, revealing striking similarity between human andAotusMHC-DRB reper-tories. Such convergence suggested that a large group of immune protection-inducing protein structures(IMPIPS), highly immunogenic and protection inducers against malarial intravenous challenge inAotus,could easily be used in humans for inducing full protection against malaria. We highlight the value of alogical and rational methodology for developing a vaccine in an appropriate animal model:Aotusmonkeys

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Browsing by Author "Suárez, Carlos F."

Assessing Peptide Binding to MHC II: An Accurate Semiempirical Quantum Mechanics Based Proposal ﻿

Babesia Bovis Ligand-Receptor Interaction: AMA-1 Contains Small Regions Governing Bovine Erythrocyte Binding ﻿

Erratum: Publisher Correction: Mass & secondary structure propensity of amino acids explain their mutability and evolutionary replacements ﻿

Major Histocompatibility Complex Class II (DRB3) Genetic Diversity in Spanish Morucha and Colombian Normande Cattle Compared to Taurine and Zebu Populations ﻿

Malaria: Paving the way to developing peptide-based vaccines against invasion in infectious diseases ﻿

Mass & secondary structure propensity of amino acids explain their mutability and evolutionary replacements ﻿

Plasmodium vivax Pv12 B-cell epitopes and HLA-DRβ1-dependent T-cell epitopes in vitro antigenicity ﻿

Semi-empirical quantum evaluation of peptide – MHC class II binding ﻿

Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans ﻿

Envíos recientes

Assessing Peptide Binding to MHC II: An Accurate Semiempirical Quantum Mechanics Based Proposal

Babesia Bovis Ligand-Receptor Interaction: AMA-1 Contains Small Regions Governing Bovine Erythrocyte Binding

Erratum: Publisher Correction: Mass & secondary structure propensity of amino acids explain their mutability and evolutionary replacements

Major Histocompatibility Complex Class II (DRB3) Genetic Diversity in Spanish Morucha and Colombian Normande Cattle Compared to Taurine and Zebu Populations

Malaria: Paving the way to developing peptide-based vaccines against invasion in infectious diseases

Mass & secondary structure propensity of amino acids explain their mutability and evolutionary replacements

Plasmodium vivax Pv12 B-cell epitopes and HLA-DRβ1-dependent T-cell epitopes in vitro antigenicity

Semi-empirical quantum evaluation of peptide – MHC class II binding

Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans

Assessing Peptide Binding to MHC II: An Accurate Semiempirical Quantum Mechanics Based Proposal

Babesia Bovis Ligand-Receptor Interaction: AMA-1 Contains Small Regions Governing Bovine Erythrocyte Binding

Erratum: Publisher Correction: Mass & secondary structure propensity of amino acids explain their mutability and evolutionary replacements

Major Histocompatibility Complex Class II (DRB3) Genetic Diversity in Spanish Morucha and Colombian Normande Cattle Compared to Taurine and Zebu Populations

Malaria: Paving the way to developing peptide-based vaccines against invasion in infectious diseases

Mass & secondary structure propensity of amino acids explain their mutability and evolutionary replacements

Plasmodium vivax Pv12 B-cell epitopes and HLA-DRβ1-dependent T-cell epitopes in vitro antigenicity

Semi-empirical quantum evaluation of peptide – MHC class II binding

Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans