Lisandra Herrera Belén | Universidad de La Frontera (original) (raw)

Papers by Lisandra Herrera Belén

Research paper thumbnail of VirusHound-I: prediction of viral proteins involved in the evasion of host adaptive immune response using the random forest algorithm and generative adversarial network for data augmentation

Briefings in Bioinformatics, Nov 21, 2023

Research paper thumbnail of MultiToxPred 1.0: a novel comprehensive tool for predicting 27 classes of protein toxins using an ensemble machine learning approach

BMC bioinformatics, Apr 12, 2024

Over the course of evolution, many organisms and microorganisms have developed the ability to exp... more Over the course of evolution, many organisms and microorganisms have developed the ability to express different types of protein toxins (PT) as part of their defense mechanisms and adaptations to the environment [1]. These proteins can be found in animals [2] and poisonous plants [3-6], as well as in pathogenic bacteria [5, 6]. PTs have a wide range of molecular targets, which has allowed them to be extensively studied

Research paper thumbnail of Review and perspective on bioinformatics tools using machine learning and deep learning for predicting antiviral peptides

Research paper thumbnail of Enzyme Engineering Strategies for the Bioenhancement of l-Asparaginase Used as a Biopharmaceutical

Research paper thumbnail of Current state of molecular and metabolic strategies for the improvement of L-asparaginase expression in heterologous systems

Frontiers in Pharmacology

Heterologous expression of L-asparaginase (L-ASNase) has become an important area of research due... more Heterologous expression of L-asparaginase (L-ASNase) has become an important area of research due to its clinical and food industry applications. This review provides a comprehensive overview of the molecular and metabolic strategies that can be used to optimize the expression of L-ASNase in heterologous systems. This article describes various approaches that have been employed to increase enzyme production, including the use of molecular tools, strain engineering, and in silico optimization. The review article highlights the critical role that rational design plays in achieving successful heterologous expression and underscores the challenges of large-scale production of L-ASNase, such as inadequate protein folding and the metabolic burden on host cells. Improved gene expression is shown to be achievable through the optimization of codon usage, synthetic promoters, transcription and translation regulation, and host strain improvement, among others. Additionally, this review provide...

Research paper thumbnail of l-Asparaginase as the gold standard in the treatment of acute lymphoblastic leukemia: a comprehensive review

Medical Oncology, Apr 15, 2023

Research paper thumbnail of Antibiotic discovery against Piscirickettsia salmonis using a combined in silico and in vitro approach

Research paper thumbnail of In Silico Design of a Chimeric Humanized L-Asparaginase

Acute lymphoblastic leukemia (ALL) is the most common cancer among children worldwide, characteri... more Acute lymphoblastic leukemia (ALL) is the most common cancer among children worldwide, characterized by an overproduction of undifferentiated lymphoblasts in the bone marrow. The treatment of choice for this disease is the enzyme L-asparaginase (ASNase) from bacterial sources. ASNase hydrolyzes circulating L-asparagine in plasma, leading to starvation of leukemic cells. The ASNase formulations of E. coli and E. chrysanthemi present notorious adverse effects, especially the immunogenicity they generate, which undermines both their effectiveness as drugs and patient safety. In this study, we developed a humanized chimeric enzyme from E. coli L-asparaginase, which would reduce the immunological problems associated with current L-asparaginase therapy. For these, the immunogenic epitopes of E. coli L-asparaginase (PDB: 3ECA) were determined and replaced with those of the less immunogenic Homo sapiens asparaginase (PDB:4O0H). The structures were modeled using the Pymol software and the ch...

Research paper thumbnail of Current state of molecular and metabolic strategies for the improvement of L-asparaginase expression in heterologous systems

L-asparaginase is one of the world’s most in-demand industrial enzymes, mainly due to its therape... more L-asparaginase is one of the world’s most in-demand industrial enzymes, mainly due to its therapeutic properties and its use in the food industry. Over the years studies have been conducted to improve its specific activity and reduce side effects, driving new discoveries that promise safer, more efficient, and cheaper drugs for consumers. However, heterologous protein modifications or expression continue to be a problem during production. Therefore, addressing bottlenecks when attempting to express modified and/or heterologous proteins using the rational design of heterologous expression systems with modified hosts could be a promising strategy to improve L-asparaginase production. Problems such as inadequate protein folding, metabolic load on host cells, codon usage bias, repetitive sequences affecting translation, heavy molecular weight and/or multi-membrane domains formation; need great attention during the development of “bio-better” proteins. In this article, we address the cur...

Research paper thumbnail of nAChR-PEP-PRED: A Robust Tool for Predicting Peptide Inhibitors of Acetylcholine Receptors Using the Random Forest Classifier

International Journal of Peptide Research and Therapeutics

Research paper thumbnail of Helicobacter pylori l-asparaginase: a study of immunogenicity from an in silico approach

Research paper thumbnail of Recent advances in the design of antimicrobial peptide conjugates

Journal of Materials Chemistry B, 2022

Antimicrobial peptides (AMPs) are ubiquitous host defense peptides characterized by their antibio... more Antimicrobial peptides (AMPs) are ubiquitous host defense peptides characterized by their antibiotic activity and lower propensity for developing resistance compared to classic antibiotics.

Research paper thumbnail of PEP-PREDNa+: A web server for prediction of highly specific peptides targeting voltage-gated Na+ channels using machine learning techniques

Computers in Biology and Medicine, 2022

Research paper thumbnail of A bioinformatics analysis of the CatSper channel in the class Actinopterygii

Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology

Research paper thumbnail of The voltage-gated T-type Ca2+ channel is key to the sperm motility of Atlantic salmon (Salmo salar)

Fish Physiology and Biochemistry

Ca2+ is a key element in the sperm activation process of Salmo salar. However, the molecular mech... more Ca2+ is a key element in the sperm activation process of Salmo salar. However, the molecular mechanisms by which this ion enters the sperm cell have been poorly studied. In this study, we examined, for the first time, the role of the voltage-gated T-type Ca2+ channel in the activation of sperm motility of Salmo salar. Using an in vitro inhibition assay, a significant decrease in total and progressive motility (P < 0.0001) was observed in Salmo salar sperm when they were treated with NNC-55-0396, a highly selective blocker. The in silico analysis showed that this blocker is docked with a strong affinity for the pore of the voltage-gated T-type calcium channel suggesting the blocking of Ca2+ ions. The results show that the T-type voltage-gated Ca2+ channel is key to sperm motility in Salmo salar.

Research paper thumbnail of The CatSper channel is present and plays a key role in sperm motility of the Atlantic salmon (Salmo salar)

Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology

Among all the Ca2+ channels, CatSper channels have been one of the most studied in sperm of diffe... more Among all the Ca2+ channels, CatSper channels have been one of the most studied in sperm of different species due to their demonstrated role in the fertilization process. In fish sperm, the calcium channel plays a key role in sperm activation. However, the functionality of the CatSper channels has not been studied in any of the fish species. For the first time, we studied the relationship of the CatSper channel with sperm motility in a fish, using Atlantic salmon (Salmo salar) as the model. The results of our study showed that the CatSper channel in Salmo salar has chemical-physical characteristics similar to those reported for mammalian CatSper channels. In this work, it was shown that Salmo salar CatSper 3 protein has a molecular weight of approximately 55-kDa similar to Homo sapiens CatSper 3. In silico analyses suggest that this channel forms a heterotetramer sensitive to the specific inhibitor HC-056456, with a binding site in the center of the pore of the CatSper channel, hindering or preventing the influx of Ca2+ ions. The in vitro assay of the sperm motility inhibition of Salmo salar with the inhibitor HC-056456 showed that sperm treated with this inhibitor significantly reduced the total and progressive motility (p < .0001), demonstrating the importance of this ionic channel for this cell. The complementation of the in silico and in vitro analyses of the present work demonstrates that the CatSper channel plays a key role in the regulation of sperm motility in Atlantic salmon.

Research paper thumbnail of Role of voltage-gated L-type calcium channel in the spermatozoa motility of Atlantic salmon (Salmo salar)

Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology

Ca2+ cations play a key role in the initiation of spermatozoa motility in Atlantic salmon (Salmo ... more Ca2+ cations play a key role in the initiation of spermatozoa motility in Atlantic salmon (Salmo salar). In this study we assess the importance of the voltage-gated L-type calcium channels in the spermatozoa motility of Atlantic salmon by combined in vitro and in silico approaches. The results of this study showed that as in other fish species, voltage-gated L-type calcium channels are significant in the spermatozoa motility of Salmo salar. The in vitro assays showed that total and progressive motilities decrease significantly (****p < .001) when Salmo salar spermatozoa are treated with verapamil, which has its binding site in the pore of the voltage-gated L-type calcium channel according to the in silico analysis.

Research paper thumbnail of TTAgP 1.0: A computational tool for the specific prediction of tumor T cell antigens

Computational Biology and Chemistry

Nowadays, cancer is considered a global pandemic and millions of people die every year because th... more Nowadays, cancer is considered a global pandemic and millions of people die every year because this disease remains a challenge for the world scientific community. Even with the efforts made to combat it, there is a growing need to discover and design new drugs and vaccines. Among these alternatives, antitumor peptides are a promising therapeutic solution to reduce the incidence of deaths caused by cancer. In the present study, we developed TTAgP, an accurate bioinformatic tool that uses the random forest algorithm for antitumor peptide predictions, which are presented in the context of MHC class I. The predictive model of TTAgP was trained and validated based on several features of 922 peptides. During the model validation we achieved sensitivity = 0.89, specificity = 0.92, accuracy = 0.90 and the Matthews correlation coefficient = 0.79 performance measures, which are indicative of a robust model. TTAgP is a fast, accurate and intuitive software focused on the prediction of tumor T cell antigens.

Research paper thumbnail of A structural in silico analysis of the immunogenicity of l-asparaginase from Escherichia coli and Erwinia carotovora

Biologicals

Modelado de la biodegradación en biorreactores de lodos de hidrocarburos totales del petróleo int... more Modelado de la biodegradación en biorreactores de lodos de hidrocarburos totales del petróleo intemperizados en suelos y sedimentos (Biodegradation modeling of sludge bioreactors of total petroleum hydrocarbons weathering in soil and sediments)

Research paper thumbnail of AntiVPP 1.0: A portable tool for prediction of antiviral peptides

Computers in Biology and Medicine

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Research paper thumbnail of VirusHound-I: prediction of viral proteins involved in the evasion of host adaptive immune response using the random forest algorithm and generative adversarial network for data augmentation

Briefings in Bioinformatics, Nov 21, 2023

Research paper thumbnail of MultiToxPred 1.0: a novel comprehensive tool for predicting 27 classes of protein toxins using an ensemble machine learning approach

BMC bioinformatics, Apr 12, 2024

Over the course of evolution, many organisms and microorganisms have developed the ability to exp... more Over the course of evolution, many organisms and microorganisms have developed the ability to express different types of protein toxins (PT) as part of their defense mechanisms and adaptations to the environment [1]. These proteins can be found in animals [2] and poisonous plants [3-6], as well as in pathogenic bacteria [5, 6]. PTs have a wide range of molecular targets, which has allowed them to be extensively studied

Research paper thumbnail of Review and perspective on bioinformatics tools using machine learning and deep learning for predicting antiviral peptides

Research paper thumbnail of Enzyme Engineering Strategies for the Bioenhancement of l-Asparaginase Used as a Biopharmaceutical

Research paper thumbnail of Current state of molecular and metabolic strategies for the improvement of L-asparaginase expression in heterologous systems

Frontiers in Pharmacology

Heterologous expression of L-asparaginase (L-ASNase) has become an important area of research due... more Heterologous expression of L-asparaginase (L-ASNase) has become an important area of research due to its clinical and food industry applications. This review provides a comprehensive overview of the molecular and metabolic strategies that can be used to optimize the expression of L-ASNase in heterologous systems. This article describes various approaches that have been employed to increase enzyme production, including the use of molecular tools, strain engineering, and in silico optimization. The review article highlights the critical role that rational design plays in achieving successful heterologous expression and underscores the challenges of large-scale production of L-ASNase, such as inadequate protein folding and the metabolic burden on host cells. Improved gene expression is shown to be achievable through the optimization of codon usage, synthetic promoters, transcription and translation regulation, and host strain improvement, among others. Additionally, this review provide...

Research paper thumbnail of l-Asparaginase as the gold standard in the treatment of acute lymphoblastic leukemia: a comprehensive review

Medical Oncology, Apr 15, 2023

Research paper thumbnail of Antibiotic discovery against Piscirickettsia salmonis using a combined in silico and in vitro approach

Research paper thumbnail of In Silico Design of a Chimeric Humanized L-Asparaginase

Acute lymphoblastic leukemia (ALL) is the most common cancer among children worldwide, characteri... more Acute lymphoblastic leukemia (ALL) is the most common cancer among children worldwide, characterized by an overproduction of undifferentiated lymphoblasts in the bone marrow. The treatment of choice for this disease is the enzyme L-asparaginase (ASNase) from bacterial sources. ASNase hydrolyzes circulating L-asparagine in plasma, leading to starvation of leukemic cells. The ASNase formulations of E. coli and E. chrysanthemi present notorious adverse effects, especially the immunogenicity they generate, which undermines both their effectiveness as drugs and patient safety. In this study, we developed a humanized chimeric enzyme from E. coli L-asparaginase, which would reduce the immunological problems associated with current L-asparaginase therapy. For these, the immunogenic epitopes of E. coli L-asparaginase (PDB: 3ECA) were determined and replaced with those of the less immunogenic Homo sapiens asparaginase (PDB:4O0H). The structures were modeled using the Pymol software and the ch...

Research paper thumbnail of Current state of molecular and metabolic strategies for the improvement of L-asparaginase expression in heterologous systems

L-asparaginase is one of the world’s most in-demand industrial enzymes, mainly due to its therape... more L-asparaginase is one of the world’s most in-demand industrial enzymes, mainly due to its therapeutic properties and its use in the food industry. Over the years studies have been conducted to improve its specific activity and reduce side effects, driving new discoveries that promise safer, more efficient, and cheaper drugs for consumers. However, heterologous protein modifications or expression continue to be a problem during production. Therefore, addressing bottlenecks when attempting to express modified and/or heterologous proteins using the rational design of heterologous expression systems with modified hosts could be a promising strategy to improve L-asparaginase production. Problems such as inadequate protein folding, metabolic load on host cells, codon usage bias, repetitive sequences affecting translation, heavy molecular weight and/or multi-membrane domains formation; need great attention during the development of “bio-better” proteins. In this article, we address the cur...

Research paper thumbnail of nAChR-PEP-PRED: A Robust Tool for Predicting Peptide Inhibitors of Acetylcholine Receptors Using the Random Forest Classifier

International Journal of Peptide Research and Therapeutics

Research paper thumbnail of Helicobacter pylori l-asparaginase: a study of immunogenicity from an in silico approach

Research paper thumbnail of Recent advances in the design of antimicrobial peptide conjugates

Journal of Materials Chemistry B, 2022

Antimicrobial peptides (AMPs) are ubiquitous host defense peptides characterized by their antibio... more Antimicrobial peptides (AMPs) are ubiquitous host defense peptides characterized by their antibiotic activity and lower propensity for developing resistance compared to classic antibiotics.

Research paper thumbnail of PEP-PREDNa+: A web server for prediction of highly specific peptides targeting voltage-gated Na+ channels using machine learning techniques

Computers in Biology and Medicine, 2022

Research paper thumbnail of A bioinformatics analysis of the CatSper channel in the class Actinopterygii

Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology

Research paper thumbnail of The voltage-gated T-type Ca2+ channel is key to the sperm motility of Atlantic salmon (Salmo salar)

Fish Physiology and Biochemistry

Ca2+ is a key element in the sperm activation process of Salmo salar. However, the molecular mech... more Ca2+ is a key element in the sperm activation process of Salmo salar. However, the molecular mechanisms by which this ion enters the sperm cell have been poorly studied. In this study, we examined, for the first time, the role of the voltage-gated T-type Ca2+ channel in the activation of sperm motility of Salmo salar. Using an in vitro inhibition assay, a significant decrease in total and progressive motility (P < 0.0001) was observed in Salmo salar sperm when they were treated with NNC-55-0396, a highly selective blocker. The in silico analysis showed that this blocker is docked with a strong affinity for the pore of the voltage-gated T-type calcium channel suggesting the blocking of Ca2+ ions. The results show that the T-type voltage-gated Ca2+ channel is key to sperm motility in Salmo salar.

Research paper thumbnail of The CatSper channel is present and plays a key role in sperm motility of the Atlantic salmon (Salmo salar)

Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology

Among all the Ca2+ channels, CatSper channels have been one of the most studied in sperm of diffe... more Among all the Ca2+ channels, CatSper channels have been one of the most studied in sperm of different species due to their demonstrated role in the fertilization process. In fish sperm, the calcium channel plays a key role in sperm activation. However, the functionality of the CatSper channels has not been studied in any of the fish species. For the first time, we studied the relationship of the CatSper channel with sperm motility in a fish, using Atlantic salmon (Salmo salar) as the model. The results of our study showed that the CatSper channel in Salmo salar has chemical-physical characteristics similar to those reported for mammalian CatSper channels. In this work, it was shown that Salmo salar CatSper 3 protein has a molecular weight of approximately 55-kDa similar to Homo sapiens CatSper 3. In silico analyses suggest that this channel forms a heterotetramer sensitive to the specific inhibitor HC-056456, with a binding site in the center of the pore of the CatSper channel, hindering or preventing the influx of Ca2+ ions. The in vitro assay of the sperm motility inhibition of Salmo salar with the inhibitor HC-056456 showed that sperm treated with this inhibitor significantly reduced the total and progressive motility (p < .0001), demonstrating the importance of this ionic channel for this cell. The complementation of the in silico and in vitro analyses of the present work demonstrates that the CatSper channel plays a key role in the regulation of sperm motility in Atlantic salmon.

Research paper thumbnail of Role of voltage-gated L-type calcium channel in the spermatozoa motility of Atlantic salmon (Salmo salar)

Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology

Ca2+ cations play a key role in the initiation of spermatozoa motility in Atlantic salmon (Salmo ... more Ca2+ cations play a key role in the initiation of spermatozoa motility in Atlantic salmon (Salmo salar). In this study we assess the importance of the voltage-gated L-type calcium channels in the spermatozoa motility of Atlantic salmon by combined in vitro and in silico approaches. The results of this study showed that as in other fish species, voltage-gated L-type calcium channels are significant in the spermatozoa motility of Salmo salar. The in vitro assays showed that total and progressive motilities decrease significantly (****p < .001) when Salmo salar spermatozoa are treated with verapamil, which has its binding site in the pore of the voltage-gated L-type calcium channel according to the in silico analysis.

Research paper thumbnail of TTAgP 1.0: A computational tool for the specific prediction of tumor T cell antigens

Computational Biology and Chemistry

Nowadays, cancer is considered a global pandemic and millions of people die every year because th... more Nowadays, cancer is considered a global pandemic and millions of people die every year because this disease remains a challenge for the world scientific community. Even with the efforts made to combat it, there is a growing need to discover and design new drugs and vaccines. Among these alternatives, antitumor peptides are a promising therapeutic solution to reduce the incidence of deaths caused by cancer. In the present study, we developed TTAgP, an accurate bioinformatic tool that uses the random forest algorithm for antitumor peptide predictions, which are presented in the context of MHC class I. The predictive model of TTAgP was trained and validated based on several features of 922 peptides. During the model validation we achieved sensitivity = 0.89, specificity = 0.92, accuracy = 0.90 and the Matthews correlation coefficient = 0.79 performance measures, which are indicative of a robust model. TTAgP is a fast, accurate and intuitive software focused on the prediction of tumor T cell antigens.

Research paper thumbnail of A structural in silico analysis of the immunogenicity of l-asparaginase from Escherichia coli and Erwinia carotovora

Biologicals

Modelado de la biodegradación en biorreactores de lodos de hidrocarburos totales del petróleo int... more Modelado de la biodegradación en biorreactores de lodos de hidrocarburos totales del petróleo intemperizados en suelos y sedimentos (Biodegradation modeling of sludge bioreactors of total petroleum hydrocarbons weathering in soil and sediments)

Research paper thumbnail of AntiVPP 1.0: A portable tool for prediction of antiviral peptides

Computers in Biology and Medicine

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.