Martínez Ríos, Félix Orlando
Thumbnail Image
Preferred name
Martínez Ríos, Félix Orlando
Official Name
Martínez Ríos, Félix Orlando
Alternative Name
fmartin
Main Affiliation
ORCID
Scopus Author ID
24339038500
Researcher ID
N-7502-2018

Research Output

Filters

6
6
6
Reset filters

Settings
Now showing 1 - 6 of 6
No Thumbnail Available
Publication

Biophysical Analysis of Potential Inhibitors of SARS-CoV-2 Cell Recognition and Their Effect on Viral Dynamics in Different Cell Types: A Computational Prediction from In Vitro Experimental Data

2024 , González-Paz, Lenin , Lossada, Carla , Hurtado-León, María Laura , Vera-Villalobos, Joan , L. Paz, José , Marrero-Ponce, Yovani , Martínez Ríos, Félix Orlando , Alvarado, Ysaías. J.

Recent reports have suggested that the susceptibility of cells to SARS-CoV-2 infection can be influenced by various proteins that potentially act as receptors for the virus. To investigate this further, we conducted simulations of viral dynamics using different cellular systems (Vero E6, HeLa, HEK293, and CaLu3) in the presence and absence of drugs (anthelmintic, ARBs, anticoagulant, serine protease inhibitor, antimalarials, and NSAID) that have been shown to impact cellular recognition by the spike protein based on experimental data. Our simulations revealed that the susceptibility of the simulated cell systems to SARS-CoV-2 infection was similar across all tested systems. Notably, CaLu3 cells exhibited the highest susceptibility to SARS-CoV-2 infection, potentially due to the presence of receptors other than ACE2, which may account for a significant portion of the observed susceptibility. Throughout the study, all tested compounds showed thermodynamically favorable and stable binding to the spike protein. Among the tested compounds, the anticoagulant nafamostat demonstrated the most favorable characteristics in terms of thermodynamics, kinetics, theoretical antiviral activity, and potential safety (toxicity) in relation to SARS-CoV-2 spike protein-mediated infections in the tested cell lines. This study provides mathematical and bioinformatic models that can aid in the identification of optimal cell lines for compound evaluation and detection, particularly in studies focused on repurposed drugs and their mechanisms of action. It is important to note that these observations should be experimentally validated, and this research is expected to inspire future quantitative experiments. ©American Chemical Society

View
No Thumbnail Available
Publication

A Novel Network Science and Similarity-Searching-Based Approach for Discovering Potential Tumor-Homing Peptides from Antimicrobials

2022 , Romero, Maylin , Marrero-Ponce, Yovani , Rodríguez, Hortensia , Agüero-Chapin, Guillermin , Antunes, Agostinho , Aguilera-Mendoza, Longendri , Martínez Ríos, Félix Orlando

Peptide-based drugs are promising anticancer candidates due to their biocompatibility and low toxicity. In particular, tumor-homing peptides (THPs) have the ability to bind specifically to cancer cell receptors and tumor vasculature. Despite their potential to develop antitumor drugs, there are few available prediction tools to assist the discovery of new THPs. Two webservers based on machine learning models are currently active, the TumorHPD and the THPep, and more recently the SCMTHP. Herein, a novel method based on network science and similarity searching implemented in the starPep toolbox is presented for THP discovery. The approach leverages from exploring the structural space of THPs with Chemical Space Networks (CSNs) and from applying centrality measures to identify the most relevant and non-redundant THP sequences within the CSN. Such THPs were considered as queries (Qs) for multi-query similarity searches that apply a group fusion (MAX-SIM rule) model. The resulting multi-query similarity searching models (SSMs) were validated with three benchmarking datasets of THPs/non-THPs. The predictions achieved accuracies that ranged from 92.64 to 99.18% and Matthews Correlation Coefficients between 0.894–0.98, outperforming state-of-the-art predictors. The best model was applied to repurpose AMPs from the starPep database as THPs, which were subsequently optimized for the TH activity. Finally, 54 promising THP leads were discovered, and their sequences were analyzed to encounter novel motifs. These results demonstrate the potential of CSNs and multi-query similarity searching for the rapid and accurate identification of THPs.

View
No Thumbnail Available
Publication

Enhancing Acute Oral Toxicity Predictions by using Consensus Modeling and Algebraic Form-Based 0D-to-2D Molecular Encodes

2019 , García-Jacas, César R. , Marrero-Ponce, Yovani , Cortés-Guzmán, Fernando , Suárez-Lezcano, José , Martínez Ríos, Félix Orlando , García-González, Luis A. , Pupo-Meriño, Mario , Martínez-Mayorga, Karina

Quantitative structure–activity relationships (QSAR) are introduced to predict acute oral toxicity (AOT), by using the QuBiLS-MAS (acronym for quadratic, bilinear and N-Linear maps based on graph-theoretic electronic-density matrices and atomic weightings) framework for the molecular encoding. Three training sets were employed to build the models: EPA training set (5931 compounds), EPA-full training set (7413 compounds), and Zhu training set (10 152 compounds). Additionally, the EPA test set (1482 compounds) was used for the validation of the QSAR models built on the EPA training set, while the ProTox (425 compounds) and T3DB (284 compounds) external sets were employed for the assessment of all the models. The k-nearest neighbor, multilayer perceptron, random forest, and support vector machine procedures were employed to build several base (individual) models. The base models with REPA–training ≥ 0.75 (R = correlation coefficient) and MAEEPA–training ≤ 0.5 (MAE = mean absolute error) were retained to build consensus models. As a result, two consensus models based on the minimum operator and denoted as M19 and M22, as well as a consensus model based on the weighted average operator and denoted as M24, were selected as the best ones for each training set considered. According to the applicability domain (AD) analysis performed, model M19 (built on the EPA training set) has MAEtest–AD = 0.4044, MAEProTox–AD = 0.4067 and MAET3DB–AD = 0.2586 on the EPA test set, ProTox external set, and T3DB external set, respectively; whereas model M22 (built on the EPA-full set) and model M24 (built on the Zhu set) present MAEProTox–AD = 0.3992 and MAET3DB–AD = 0.2286, and MAEProTox–AD = 0.3773 and MAET3DB–AD = 0.2471 on the two external sets accounted for, respectively. These outcomes were compared and statistically validated with respect to 14 QSAR methods (e.g., admetSAR, ProTox-II) from the literature. As a result, model M22 presents the best overall performance. In addition, a retrospective study on 261 withdrawn drugs due to their toxic/side effects was performed, to assess the usefulness of prospectively using the QSAR models proposed in the labeling of chemicals. A comparison with regard to the methods from the literature was also made. As a result, model M22 has the best ability of labeling a compound as toxic according to the globally harmonized system of classification and labeling of chemicals. Therefore, it can be concluded that the models proposed, especially model M22, constitute prominent tools for studying AOT, at providing the best results among all the methods examined. A freely available software was also developed to be used in virtual screening tasks (http://tomocomd.com/apps/ptoxra).

View
No Thumbnail Available
Publication

StarPep Toolbox: an open-source software to assist chemical space analysis of bioactive peptides and their functions using complex networks

2023 , Aguilera-Mendoza, Longendri , Ayala-Ruano, Sebastián , Martínez Ríos, Félix Orlando , Chávez, Edgar , García-Jacas, César R. , Brizuela, Carlos A. , Marrero-Ponce, Yovani

Motivation: Antimicrobial peptides (AMPs) are promising molecules to treat infectious diseases caused by multi-drug resistance pathogens, some types of cancer, and other conditions. Computer-aided strategies are efficient tools for the high-throughput screening of AMPs. Copyright © 2024 Oxford University Press

View
No Thumbnail Available
Publication

Rethinking the applicability domain analysis in QSAR models

2024 , Mora, Jose R. , Marquez, Edgar A. , Pérez-Pérez, Noel , Contreras-Torres, Ernesto , Perez-Castillo, Yunierkis , Agüero-Chapin, Guillermin , Martínez Ríos, Félix Orlando , Marrero-Ponce, Yovani , Barigye, Stephen J.

Notwithstanding the wide adoption of the OECD principles (or best practices) for QSAR modeling, disparities between in silico predictions and experimental results are frequent, suggesting that model predictions are often too optimistic. Of these OECD principles, the applicability domain (AD) estimation has been recognized in several reports in the literature to be one of the most challenging, implying that the actual reliability measures of model predictions are often unreliable. Applying tree-based error analysis workflows on 5 QSAR models reported in the literature and available in the QsarDB repository, i.e., androgen receptor bioactivity (agonists, antagonists, and binders, respectively) and membrane permeability (highest membrane permeability and the intrinsic permeability), we demonstrate that predictions erroneously tagged as reliable (AD prediction errors) overwhelmingly correspond to instances in subspaces (cohorts) with the highest prediction error rates, highlighting the inhomogeneity of the AD space. In this sense, we call for more stringent AD analysis guidelines which require the incorporation of model error analysis schemes, to provide critical insight on the reliability of underlying AD algorithms. Additionally, any selected AD method should be rigorously validated to demonstrate its suitability for the model space over which it is applied. These steps will ultimately contribute to more accurate estimations of the reliability of model predictions. Finally, error analysis may also be useful in “rational” model refinement in that data expansion efforts and model retraining are focused on cohorts with the highest error rates. © 2024 Springer Nature

View
No Thumbnail Available
Publication

Complex Networks Analyses of Antibiofilm Peptides: An Emerging Tool for Next-Generation Antimicrobials’ Discovery

2023 , Agüero-Chapin, Guillermin , Antunes, Agostinho , Mora, José R. , Pérez, Noel , Contreras-Torres, Ernesto , Valdes-Martini, José R. , Martínez Ríos, Félix Orlando , Zambrano, Cesar H. , Marrero-Ponce, Yovani

Microbial biofilms cause several environmental and industrial issues, even affecting human health. Although they have long represented a threat due to their resistance to antibiotics, there are currently no approved antibiofilm agents for clinical treatments. The multi-functionality of antimicrobial peptides (AMPs), including their antibiofilm activity and their potential to target multiple microbes, has motivated the synthesis of AMPs and their relatives for developing antibiofilm agents for clinical purposes. Antibiofilm peptides (ABFPs) have been organized in databases that have allowed the building of prediction tools which have assisted in the discovery/design of new antibiofilm agents. However, the complex network approach has not yet been explored as an assistant tool for this aim. Herein, a kind of similarity network called the half-space proximal network (HSPN) is applied to represent/analyze the chemical space of ABFPs, aiming to identify privileged scaffolds for the development of next-generation antimicrobials that are able to target both planktonic and biofilm microbial forms. Such analyses also considered the metadata associated with the ABFPs, such as origin, other activities, targets, etc., in which the relationships were projected by multilayer networks called metadata networks (METNs). From the complex networks’ mining, a reduced but informative set of 66 ABFPs was extracted, representing the original antibiofilm space. This subset contained the most central to atypical ABFPs, some of them having the desired properties for developing next-generation antimicrobials. Therefore, this subset is advisable for assisting the search for/design of both new antibiofilms and antimicrobial agents. The provided ABFP motifs list, discovered within the HSPN communities, is also useful for the same purpose. © 2023 by the authors.

View