Julio Caballero

Julio Caballero
Universidad de Talca · Faculty of Engineering

Associate Professor

About

182
Publications
29,010
Reads
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3,978
Citations
Citations since 2016
81 Research Items
2130 Citations
20162017201820192020202120220100200300400
20162017201820192020202120220100200300400
20162017201820192020202120220100200300400
20162017201820192020202120220100200300400
Additional affiliations
January 2012 - present
Universidad de Talca
Position
  • Professor (Associate)

Publications

Publications (182)
Article
Full-text available
The design of TRPV1 antagonists and agonists has reached a new era since TRPV1 structures at near-atomic resolution are available. Today, the ligand-binding forms of several classical antagonists and agonists are known; therefore, the specific role of key TRPV1’s residues in binding of ligands can be elucidated. It is possible to place the well-def...
Article
Motivation: The term clustering designates a comprehensive family of unsupervised learning methods allowing to group similar elements into sets called clusters. Geometrical clustering of Molecular Dynamics (MD) trajectories is awell-established analysis to gain insights into the conformational behavior of simulated systems. However, popular varian...
Article
Motivation Density Peaks is a widely spread clustering algorithm that has been previously applied to Molecular Dynamics simulations. Its conception of cluster centers as elements displaying both a high density of neighbors and a large distance to other elements of high density, particularly fits the nature of a geometrical converged Molecular Dynam...
Article
Full-text available
Parkinson's disease (PD) is a neurodegenerative disorder that affects adult people whose treatment is palliative. Thus, we decided to test three dammarane triterpenes 1, 1a, 1b, and we determined that 1 and 1a inhibit β-aggregation through thioflavine T rather than 1b. Since compound 1 was most active, we determined the interaction between α-synucl...
Article
Motivation Classical Molecular Dynamics is a standard computational approach to model time-dependent processes at the atomic level. The inherent sparsity of increasingly huge generated trajectories demands clustering algorithms to reduce other post-simulation analysis complexity. The quality threshold (QT) variant is an appealing one from the vast...
Article
The secondary structure is important in protein structure analysis, classification, and modeling. We have developed a novel method for secondary structure assignment, termed PSIQUE, based on the potential energy surface (PES) of polyalanine obtained using an infinitely long chain model and density functional theory calculations. First, uniform prot...
Article
Full-text available
Several years ago, the crystallographic structures of the transient receptor potential vanilloid 1 (TRPV1) in the presence of agonists and antagonists were reported, providing structural information about its chemical activation and inactivation. TRPV1’s activation increases the transport of calcium and sodium ions, leading to the excitation of sen...
Conference Paper
Dipeptides self-assemble into higher-order structures that can function as biomaterials for a wide range of applications in the nanotechnology and biomedical fields. Some hydrophobic L-dipeptides like FF, LF, AV or VV assemble into helical nanotubes whose pores can be either hydrophobic (type I, e.g., AV and VV) or hydrophilic (type II, e. g. FF an...
Article
Introduction Molecular docking has been consolidated as one of the most important methods in the molecular modeling field. It has been recognized as a prominent tool in the study of protein-ligand complexes, to describe intermolecular interactions, to accurately predict poses of multiple ligands, to discover novel promising bioactive compounds. Mol...
Article
Evaluating the availability of molecular oxygen (O2) and energy of excited states in the retinal binding site of rhodopsin is a crucial challenging first step to understand photosensitizing reactions in wild‐type (WT) and mutant rhodopsins by absorbing visible light. In the present work, energies of the ground and excited states related to 11‐cis ‐...
Article
Although molecular dynamics simulations allow for the study of interactions among virtually all biomolecular entities, metal ions still pose significant challenges in achieving an accurate structural and dynamical description of many biological assemblies, particularly to coarse-grained (CG) models. Although the reduced computational cost of CG met...
Article
We present here a detailed theoretical analysis of L-arginine hydrolysis catalyzed by Human Arginase I (HARGI). Our study combines classical molecular dynamic simulations of different model for the enzyme-substrate complex and a detailed exploration of the reaction mechanism for the most plausible model, using hybrid QM/MM techniques. Different enz...
Preprint
p>Although molecular dynamics simulations allow for the study of interactions among virtually all biomolecular entities, metal ions still pose significant challenges to achieve an accurate structural and dynamical description of many biological assemblies. This is particularly the case for coarse-grained (CG) models. Although the reduced computatio...
Article
Motivation Root Mean Square Deviation (RMSD) is one of the most useful and straightforward features for structural comparison between different conformations of the same molecule. Commonly, protein-ligand docking programs have included some utilities that allow the calculation of this value; however, they only work efficiently when exists a complet...
Article
Full-text available
The angiotensin-converting enzyme (ACE) is a two-domain dipeptidylcarboxypeptidase, which has a direct involvement in the control of blood pressure by performing the hydrolysis of angiotensin I to produce angiotensin II. At the same time, ACE hydrolyzes other substrates such as the vasodilator peptide bradykinin and the anti-inflammatory peptide N-...
Article
The two-domain dipeptidylcarboxypeptidase Angiotensin-I-converting enzyme (EC 3.4.15.1; ACE) plays an important physiological role in blood pressure regulation via the renin-angiotensin and kallikrein-kinin systems by converting angiotensin I to the potent vasoconstrictor angiotensin II, and by cleaving a number of other substrates including the va...
Article
Significant progresses have been made to understand the molecular basis of the Sigma1 receptor (S1R) operating in normal and pathological conditions. S1R is a transmembrane protein that participates in a wide variety of processes at the central nervous system; hence, its function has been associated with mental and neurological disorders. Several l...
Article
Full-text available
The zinc metallopeptidase Pseudomonas elastase (LasB) is a virulence factor of Pseudomonas aeruginosa (P. aeruginosa), a pathogenic bacterium that can cause nosocomial infections. The present study relates the structural analysis of 118 N-alpha-mercaptoacetyl dipeptides (NAMdPs) as LasB inhibitors. Field-based 3D-QSAR and molecular docking methods...
Article
Full-text available
The growing computational capacity allows the investigation of large biomolecular systems by increasingly extensive molecular dynamics simulations. The resulting huge trajectories demand efficient partition methods to discern relevant structural dissimilarity. Clustering algorithms are available to address this task, but their implementations still...
Article
Full-text available
Clustering Molecular Dynamics trajectories is a common analysis that allows grouping together similar conformations. Several algorithms have been designed and optimized to perform this routine task and amongst them, Quality Threshold stands as a very attractive option. This algorithm guarantees that in retrieved clusters, no pair of frames will hav...
Article
Full-text available
Cyclin-dependent kinase 2 (CDK2) is an important member of the CDK family exerting its most important function in the regulation of the cell cycle. It catalyzes the transfer of the gamma phosphate group from an ATP (adenosine triphosphate) molecule to a Serine/Threonine residue of a peptide substrate. Due to the importance of this enzyme, and prote...
Article
Full-text available
TASK-3 is a two-pore domain potassium (K2P) channel highly expressed in the hippocampus, cerebellum, and cortex. TASK-3 has been identified as an oncogenic potassium channel and it is overexpressed in different cancer types. For this reason, the development of new TASK-3 blockers could influence the pharmacological treatment of cancer and several n...
Article
Jasmonates are fatty acid derivatives that control several plant processes including growth, development and defense. Despite the chemical diversity of jasmonates, only jasmonoyl-L-isoleucine (JA-Ile) has been clearly characterized as the endogenous ligand of the jasmonate co-receptors (COI1-JAZs) in higher plants. Currently, it is accepted that ω-...
Article
The current work provides a study on the cis–trans isomerization behaviour of N–alkylated peptides decorated with phosphonate ester group. Ugi four-component reaction was chosen for the synthesis of N–alkylated peptides, where almost only the cis isomer was detected when the phosphonate ester group was incorporated as amine component in the side ch...
Article
Full-text available
The human Sigma1 receptor (S1R), which has been identified as a target with an important role in neuropsychological disorders, was first crystallized 3 years ago. Since S1R structure has no relation with another previous crystallized structures, the presence of the new crystal is an important hallmark for the design of agonists and antagonists agai...
Article
The crystal structure of the salt produced by the reaction of pyrimethamine (an antimalarial 14 drug) with 2-hydroxy-3,5-dinitrobenzoic acid [systematic name: 2,4-diamino-5-(4- 15 chlorophenyl)-6-ethylpyrimidin-1-ium 2-hydroxy-3,5-dinitrobenzoate] has been investigated 16 using X-rays diffraction data collected at room temperature. The results s...
Preprint
Full-text available
Cyclin-dependent kinase 2 (CDK2) is an important member of the CDK family exerting its most important function in the regulation of the cell cycle. It catalyzes the transfer of the gamma phosphate group from an ATP (adenosine triphosphate) molecule to a Serine/Threonine residue of a peptide substrate. Due to the importance of this enzyme, and prote...
Article
Transient receptor potential vanilloid 1 (TRPV1) is a polymodal cation channel activated by heat, voltage, and ligands. Also known as the capsaicin receptor, TRPV1 is expressed in numerous tissues by different cell types, including peripheral sensory fibers where acts as a thermal and chemical detector in nociceptive pathways. TRPV1 channels are ab...
Article
Full-text available
Phosphofructokinases (Pfks) catalyze the ATP-dependent phosphorylation of fructose-6-phosphate (F6P) and they are regulated in a wide variety of organisms. Although numerous aspects of the kinetics and regulation have been characterized for Pfks, the knowledge about the mechanism of the phosphoryl 15 transfer reaction and the transition state lags...
Article
Full-text available
Ugi four component reaction (Ugi-4CR) isocyanide-based multicomponent reactions were used to synthesize diN-substituted glycyl-phenylalanine (diNsGF) derivatives. All of the synthesized compounds were characterized by spectroscopic and spectrometric techniques. In order to evaluate potential biological applications, the synthesized compounds were t...
Article
Full-text available
Most snake venom toxins are proteins, and participate to envenomation through a diverse array of bioactivities, such as bleeding, inflammation, and pain, cytotoxic, cardiotoxic or neurotoxic effects. The venom of a single snake species contains hundreds of toxins, and the venoms of the 725 species of venomous snakes represent a large pool of potent...
Article
Full-text available
In the last decades, human protein kinases (PKs) have been relevant as targets in the development of novel therapies against many diseases, but the study of Mycobacterium tuberculosis PKs (MTPKs) involved in tuberculosis pathogenesis began much later and has not yet reached an advanced stage of development. To increase knowledge of these enzymes, i...
Article
Two approaches of building up predictive models for acetylcholinesterase inhibitory activity of a broad dataset of 403 compounds, 2D Autocorrelation descriptors and 2D Monte Carlo descriptors, were compared. In a first approach, the molecular information has been encoded in 2D autocorrelation descriptors, obtained from different weighting schemes....
Article
Full-text available
Alzheimer´s disease (AD) is the most common form of dementia involving Aβ and tau protein. So far, AD cure remains elusive, but considering that AD progresses throughout tau pathology, which turns tau protein an appropriate target, besides tau is also included in other neurodegenerative disorders named as tauopathies. Here, we have isolated sevente...
Article
Full-text available
Human arginase I (hARGI) is an important enzyme involved in the urea cycle; its overexpression has been associated to cardiovascular and cerebrovascular diseases. In the last years, several congeneric sets of hARGI inhibitors have been reported with possible beneficial roles for the cardiovascular system. At the same time, crystallographic data hav...
Article
Plants from temperate climates, such as the model plant Arabidopsis thaliana, are challenged with seasonal low temperatures that lead to increased freezing tolerance in fall in a process termed cold acclimation. Among other adaptations, this involves the accumulation of cold-regulated (COR) proteins, such as the intrinsically disordered chloroplast...
Article
Full-text available
Two-pore domain (K2P) channels are twofold symmetric K⁺ channels which control cell excitability by enabling the leak of potassium ions from cells in response to physicochemical stimuli. Crystallization of K2P channels revealed the presence of several structural features, which include an external cap. In the available crystallographic structures,...
Article
Full-text available
Molecular docking is the most frequently used computational method for studying the interactions between organic molecules and biological macromolecules. In this context, docking allows predicting the preferred pose of a ligand inside a receptor binding site. However, the selection of the "best" solution is not a trivial task, despite the widely ac...
Article
We studied the chemical entities within N-octanoyl dopamine (NOD) responsible for transient receptor potential channels of the vanilloid receptor subtype 1 (TRPV1) activation and inhibition of inflammation. The efficacy of NOD to activate TRPV1 was significantly higher compared to variants in which the ortho-dihydroxy groups were acetylated, one of...
Article
Protein kinases (PKs) discriminate between closely related sequences that contain serine, threonine, and/or tyrosine residues. Such specificity is defined by the amino acid sequence surrounding the phosphorylatable residue, so that it is possible to identify an optimal recognition motif (ORM) for each PK. The ORM for the protein kinase A (PKA), a w...
Article
Full-text available
This study describes the in-silico design, synthesis, and evaluation of a cross-linked PVA hydrogel (CLPH) for the absorption of organophosphorus pesticide dimethoate from aqueous solutions. The crosslinking effectiveness of 14 dicarboxilic acids was evaluated through in-silico studies using semiempirical quantum mechanical calculations. According...
Chapter
Proline-directed protein kinases (PDPKs) are protein kinases (PKs) that phosphorylate serine or threonine preceding a proline residue (S/TP motif). It is known that these enzymes are responsible for tau hyperphosphorylation, which is related to the formation of amyloid plaques (APs) and neurofibrillary tangles (NFTs) in Alzheimer’s disease (AD) pat...
Article
Full-text available
PDE3s belong to the phosphodiesterases family, where the PDE3A isoform is the major subtype in platelets involved in the cAMP regulation pathway of platelet aggregation. PDE3A inhibitors have been designed as potential antiplatelet agents. In this work, a homology model of PDE3A was developed and used to obtain the binding modes of bicyclic heteroa...
Data
Structures and activities of the studied PDE3A inhibitors, information about the distribution of the activity values, equilibration of MD simulations, and residual plots between predicted and experimental values for the FQSAR models. (DOCX)
Article
Selected adenosine A2A receptor agonists (PSB-15826, PSB-12404, and PSB-16301) have been evaluated as new antiplatelet agents. In addition, radioligand-binding studies and receptor-docking experiments were performed in order to explain their differential biological effects on a molecular level. Among the tested adenosine derivatives, PSB-15826 was...
Article
Full-text available
The potassium channel AKT2 plays important roles in phloem loading and unloading. It can operate as inward-rectifying channel that allows H+-ATPase-energized K+ uptake. Moreover, through reversible post-translational modifications it can also function as an open, K+-selective channel, which taps a ‘potassium battery’, providing additional energy fo...
Article
One of the primary goals of applied proteomics is the development of new computational methods for modeling the properties of the proteins from the primary structure. In this work, we used the concept of semi-supervised learning, which is relatively new machine learning philosophy that combines labeled and unlabeled instances simultaneously, to per...
Chapter
Artificial neural networks (ANNs) are often used “in silico” drug design for correlation, classification, and prediction of the activity of bioactive compounds and drug. In this chapter, we approach the implementation of Bayesian-regularized artificial neural networks (BRANNs) combined with genetic algorithm (GA) feature selection, so-called Bayesi...
Article
Sampatrilat is a vasopeptidase inhibitor that inhibits both angiotensin I-converting enzyme (ACE) and neutral endopeptidase (NEP). ACE is a zinc dipeptidyl carboxypeptidase that contains two extracellular domains (nACE and cACE). In this study the molecular basis for the selectivity of sampatrilat for nACE and cACE was investigated. Enzyme inhibiti...
Conference Paper
Protein kinases (PKs) constitute a large and diverse family of enzymes that modify other proteins (substrates) by phosphorylation, which is crucial for cell-division regulation, metabolic routes regulation, and many other cellular functions.¹ A malfunction in such regulation processes can lead to several diseases like inflammatory disorders, endocr...
Article
To mitigate pre-transplantation injury in organs of potential donors N-octanoyl dopamine (NOD) treatment might be considered as it does not affect hemodynamic parameters in brain dead (BD) donors. To better assess optimal NOD concentrations for donor treatment, we report on the fast and facile radiofluorination of the NOD-derivative [¹⁸F]F-NOD [¹⁸F...
Article
Full-text available
It is evident that 99mTc causes radical-mediated DNA damage due to Auger electrons, which were emitted simultaneously with the known γ-emission of 99mTc. We have synthesized a series of new 99mTc-labeled pyrene derivatives with varied distances between the pyrene moiety and the radionuclide. The pyrene motif is a common DNA intercalator and allowed...
Article
Full-text available
In the last years, the interactions of flavonoids with protein kinases (PKs) have been described by using crystallographic experiments. Interestingly, different orientations have been found for one flavonoid inside different PKs and different chemical substitutions lead to different orientations of the flavonoid scaffold inside one PK. Accordingly,...
Article
Full-text available
Liquid chromatography coupled with mass spectrometry is an outstanding methodology for fast analysis of phenolic compounds in biological samples. Twenty two compounds were quickly and accurately identified in the methanolic extract of the Antarctic lichen Ramalina terebrata for the first time using ultra high pressure liquid chromatography coupled...
Article
The peroxisome proliferator-activated receptors (PPARs) comprise a family of three nuclear receptor isoforms (γ, β/δ, α) which are key regulators of metabolism and inflammation. A series of potent PPARγ agonists with high chemical diversity and variable activities have been reported in recent years; however, few molecular atomistic studies have bee...