Dinler Antunes

Dinler Antunes
Rice University · Department of Computer Science

PhD

About

49
Publications
8,161
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Citations
Introduction
Dinler Antunes is a Postdoctoral Research Associate at the Computer Science Department of Rice University (Houston, TX), interested in structural bioinformatics and immunology. He is developing new computational methods for structural modeling and structural analysis of protein-ligand complexes that play key roles in cellular immunity. His work will facilitate the development of safer and better personalized immunotherapy treatments for cancer, having also applications for vaccinology and autoimmunity. Additional information at dinlerantunes.com
Additional affiliations
October 2015 - present
Rice University
Position
  • PhD Student
October 2014 - September 2015
Rice University
Position
  • PhD Student
June 2011 - August 2014
Universidade Federal do Rio Grande do Sul
Position
  • PhD Student

Publications

Publications (49)
Article
Full-text available
Human leukocyte antigen class I (HLA-I) molecules bind and present peptides at the cell surface to facilitate the induction of appropriate CD8 + T cell-mediated immune responses to pathogen- and self-derived proteins. The HLA-I peptide-binding cleft contains dominant anchor sites in the B and F pockets that interact primarily with amino acids at pe...
Article
Full-text available
Data produced by hydrogen-exchange monitoring experiments have been used in structural studies of molecules for several decades. Despite uncertainties about the structural determinants of hydrogen exchange itself, such data have successfully helped guide the structural modeling of challenging molecular systems, such as membrane proteins or large ma...
Article
Full-text available
An unprecedented research effort has been undertaken in response to the ongoing COVID-19 pandemic. This has included the determination of hundreds of crystallographic structures of SARS-CoV-2 proteins, and numerous virtual screening projects searching large compound libraries for potential drug inhibitors. Unfortunately, these initiatives have had...
Preprint
Motivation Recent efforts to computationally identify inhibitors for SARS-CoV-2 proteins have largely ignored the issue of receptor flexibility. We have implemented a computational tool for ensemble docking with the SARS-CoV-2 proteins, including the main protease (Mpro), papain-like protease (PLpro) and RNA-dependent RNA polymerase (RdRp). Result...
Article
Significance Peptide binding to MHC receptors is part of a central biological process that enables our immune system to attack diseased cells. We use molecular simulations to illuminate the mechanisms driving stable peptide–MHC binding. Our simulation framework produces an atomistic model of the unbinding dynamics for a given peptide–MHC, which qua...
Article
Full-text available
HLA-G is considered to be an immune checkpoint molecule, a function that is closely linked to the structure and dynamics of the different HLA-G isoforms. Unfortunately, little is known about the structure and dynamics of these isoforms. For instance, there are only seven crystal structures of HLA-G molecules, being all related to a single isoform,...
Article
Full-text available
The complement system plays a major role in human immunity, but its abnormal activation can have severe pathological impacts. By mimicking a natural mechanism of complement regulation, the small peptide compstatin has proven to be a very promising complement inhibitor. Over the years, several compstatin analogs have been created, with improved inhi...
Article
Full-text available
Prediction of stable peptide binding to Class I HLAs is an important component for designing immunotherapies. While the best performing predictors are based on machine learning algorithms trained on peptide-HLA (pHLA) sequences, the use of structure for training predictors deserves further exploration. Given enough pHLA structures, a predictor base...
Article
Full-text available
PURPOSE HLA protein receptors play a key role in cellular immunity. They bind intracellular peptides and display them for recognition by T-cell lymphocytes. Because T-cell activation is partially driven by structural features of these peptide-HLA complexes, their structural modeling and analysis are becoming central components of cancer immunothera...
Article
Full-text available
Background: Docking large ligands, and especially peptides, to protein receptors is still considered a challenge in computational structural biology. Besides the issue of accurately scoring the binding modes of a protein-ligand complex produced by a molecular docking tool, the conformational sampling of a large ligand is also often considered a ch...
Article
Full-text available
The Class I Major Histocompatibility Complex (MHC) is a central protein in immunology as it binds to intracellular peptides and displays them at the cell surface for recognition by T-cells. The structural analysis of bound peptide-MHC complexes (pMHCs) holds the promise of interpretable and general binding prediction (i.e., testing whether a given...
Article
Full-text available
Understanding the mechanisms involved in the activation of an immune response is essential to many fields in human health, including vaccine development and personalized cancer immunotherapy. A central step in the activation of the adaptive immune response is the recognition, by T-cell lymphocytes, of peptides displayed by a special type of recepto...
Article
Full-text available
Both experimental and computational methods are available to gather information about a protein’s conformational space and interpret changes in protein structure. However, experimentally observing and computationally modeling large proteins remain critical challenges for structural biology. Our work aims at addressing these challenges by combining...
Article
Full-text available
The class I major histocompatibility complex (MHC) is capable of binding peptides derived from intracellular proteins and displaying them at the cell surface. The recognition of these peptide-MHC (pMHC) complexes by T-cells is the cornerstone of cellular immunity, enabling the elimination of infected or tumoral cells. T-cell-based immunotherapies a...
Article
Full-text available
Hydrogen/deuterium exchange detected by mass spectrometry (HDX-MS) provides valuable information on protein structure and dynamics. Although HDX-MS data is often interpreted using crystal structures, it was suggested that conformational ensembles produced by molecular dynamics simulations yield more accurate interpretations. In this paper, we analy...
Article
Full-text available
Immunotherapy has become one of the most promising avenues for cancer treatment, making use of the patient’s own immune system to eliminate cancer cells. Clinical trials with T-cell-based immunotherapies have shown dramatic tumor regressions, being effective in multiple cancer types and for many different patients. Unfortunately, this progress was...
Article
Full-text available
Molecular docking is a standard computational approach to predict binding modes of protein-ligand complexes, by exploring alternative orientations and conformations of the ligand (i.e., by exploring ligand flexibility). Docking tools are largely used for virtual screening of small drug-like molecules, but their accuracy and efficiency greatly decay...
Article
Full-text available
Monitoring hydrogen/deuterium exchange (HDX) undergone by a protein in solution produces experimental data that translates into valuable information about the protein's structure. Data produced by HDX experiments is often interpreted using a crystal structure of the protein, when available. However, it has been shown that the correspondence between...
Article
Full-text available
The immune system is constantly challenged, being required to protect the organism against a wide variety of infectious pathogens and, at the same time, to avoid autoimmune disorders. One of the most important molecules involved in these events is the Major Histocompatibility Complex class I (MHC-I), responsible for binding and presenting small pep...
Article
Full-text available
Introduction: Protein-ligand interactions play key roles in various metabolic pathways, and the proteins involved in these interactions represent major targets for drug discovery. Molecular docking is widely used to predict the structure of protein-ligand complexes, and protein flexibility stands out as one of the most important and challenging is...
Article
Cytotoxic T-lymphocytes (CTLs) are the key players of adaptive cellular immunity, being able to identify and eliminate infected cells through the interaction with peptide-loaded major histocompatibility complexes class I (pMHC-I). Despite the high specificity of this interaction, a given lymphocyte is actually able to recognize more than just one p...
Article
Full-text available
Unlabelled: T cell responses play a critical role in controlling or clearing viruses. Therefore, strategies to prevent or treat infections include boosting T cell responses. T cells specific for various pathogens have been reported in unexposed individuals and an influence of such cells on the response toward vaccines is conceivable. However, litt...
Article
Human α-l-iduronidase (IDUA) is a member of glycoside hydrolase family and is involved in the catabolism of glycosaminoglycans (GAGs), heparan sulfate (HS) and dermatan sulfate (DS). Mutations in this enzyme are responsible for mucopolysaccharidosis I (MPS I), an inherited lysosomal storage disorder. Despite great interest in determining and studyi...
Article
Full-text available
The Human Immunodeficiency Virus type 1 protease enzyme (HIV-1 PR) is one of the most important targets of antiretroviral therapy used in the treatment of AIDS patients. The success of protease-inhibitors (PIs), however, is often limited by the emergence of protease mutations that can confer resistance to a specific drug, or even to multiple PIs. I...
Article
Full-text available
The CrossTope is a highly curate repository of three-dimensional structures of peptide:major histocompatibility complex (MHC) class I complexes (pMHC-I). The complexes hosted by this databank were obtained in protein databases and by large-scale in silico construction of pMHC-I structures, using a new approach developed by our group. At this moment...
Article
Bioinformatics is a new field of research, with roots in computer science, physics, statistics and molecular biology. Its growth was fueled by the genome sequencing initiatives and the great amount of data produced by them, having quickly spread to all other fields of biological research. This innovative way of making science proved to be especiall...
Article
The Bunyaviridae virus family is composed by five genera, of which the Hantavirus genus is one of the most important representatives. Occasionally, these viruses can be transmitted to humans, giving rise to severe diseases that present high mortality rates. We analyzed the amino acid sequences of the nucleocapsid (N) proteins of 34 different hantav...
Article
Full-text available
Bovine herpesvirus type 5 (BoHV-5) is the causative agent of bovine herpetic encephalitis. In countries where BoHV-5 is prevalent, attempts to vaccinate cattle to prevent clinical signs from BoHV-5-induced disease have relied essentially on vaccination with BoHV-1 vaccines. However, such practice has been shown not to confer full protection to BoHV...
Article
Since the beginning of studies about immune response stimulation against viral infections, many pieces have already been added to complete this puzzle. Once uncovered, it will provide the key elements to the development of more efficient vaccines against a wide diversity of infectious diseases. A thorough understanding of this system involves not o...
Data
List of ligands used to identify HLA-restricted patterns. (0.09 MB DOC)
Data
List of H-2Kb ligands available at PDB. (0.04 MB DOC)
Data
Topology of H2-Db and H2-Kb binding clefts. A: Crystal structure of an H-2Db allele (PDB access code 1CE6) is depicted as Ribbon and Surface. Epitopes inside the cleft are depicted as Sticks. Two tryptophanes of the MHC alpha-chain (W73 and W147) almost block the cleft, forcing the peptide to pass above them. B: Crystal structure of an H-2Kb allele...
Data
Conformational patterns of human MHC alleles. A: Thirty-four HLA-A*0201-restricted peptides (Table S1) were superposed using SPDBv program. Peptides sharing an A*0201-restricted pattern are depicted in blue. Exceptions to this pattern are depicted in cyan. Cancer-related peptides are depicted in light pink. Epitopes 1I7R and 1I7T are depicted in re...
Data
Structural organization of the H-2Db-restricted epitopes. A: Images of HBsAg30-39 epitope (presented in Ball and Stick_CPK) in the cleft of the H-2Db-allele (represented as surface, with negatively (red) and positively (blue) charged regions with a scale from −10 to +10 kiloteslas). Partial N-terminal ending of the epitope is hidden under MHC side...
Data
Analyze of HCV alanine exchanged peptides. The wild type HCV derived peptide (CINGVCWTV) and nine alanine exchanged peptides were analyzed. A: Sequences of 10 peptides are indicated. Level of IFN-Î3 production by CVNGVCWTV-specific CD8+ T-cells, induced by each sequence, are also represented [13]. Each bar (in black) represents the number of the Sp...
Data
Flowchart of a new pMHC complex construction. ASA values of the wild type HCV derived peptide (CVNGVCWTV) and 28 naturally occurring NS31073-variants were analyzed. In agreement with experimental data, the ASA values from genotype 6 presented the same pattern of the wild type peptide and the peptides with higher deviation from this “ASA pattern” (G...
Data
Flowchart of a new pMHC complex construction. Consider an epitope “C” whose structure in the context of a given MHC allele was not determined. A search at PDB is performed, looking for a PDB file containing the allele of interest presenting an epitope with the same length of the “c” epitope. In this example, we found the “A” complex. Using the SPDB...
Data
Exception to the H-2Db pattern. A: The 1BZ9 epitope (red) does not have the conventional amino acid in the anchor position (p5) and showed a significant deviation in the main chain when compared to other epitopes. B: The side chains of the epitope 1BZ9 (red) are in a similar conformation to other epitopes of this allele, except in a phenylalanine a...
Data
Structural pattern of H-2Kb restricted ligands. A: Twenty-two epitopes (see Table S2) restricted to this allele were superposed, four 9-mer (red) and 18 8-mer (blue). The H-2Kb restricted ligands, just like those restricted to the H-2Db allele, presented a higher identity in the side chains of the anchor positions than in the side chains oriented o...
Article
Full-text available
The immune system is engaged in a constant antigenic surveillance through the Major Histocompatibility Complex (MHC) class I antigen presentation pathway. This is an efficient mechanism for detection of intracellular infections, especially viral ones. In this work we describe conformational patterns shared by epitopes presented by a given MHC allel...
Article
Full-text available
This study was carried out to determine whether the sensitivity of serum neutralization (SN) tests would be affected by the use of distinct subtypes of bovine herpesvirus 1 (BoHV-1) and 5 (BoHV-5) as test challenge viruses. Bovine sera collected from a randomized sample (n=287) were tested in a 24h incubation SN against three type 1 viruses (BoHV-1...
Conference Paper
Hantaviruses, members of the Bunyaviridae family, are enveloped negative-stranded RNA viruses with tripartite genomes – S, M and L. The S genome codes for a nucleocapsid (N) protein, which is quite conserved among different species of the hantavirus genus and possess a recognized immunogenicity. In this work we analyzed the sequence of two regions...

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Projects

Projects (7)
Project
Developing tools for ensemble docking with SARS-CoV-2 proteins. Study PPI and protein-ligand interactions.
Project
Scientific contributions having a connection with research on the SARS-CoV-2 virus and the implications of developing COVID-19.
Project
We are developing an innovative meta-docking tool, called DINC, for the accurate docking of large ligands to protein receptors. DINC is based on an incremental and multi-threaded approach involving other molecular docking tools. Our research focuses on the challenges related to the sampling and scoring of large ligands, such as peptides.