Plant-antivenom: Database of anti-venom medicinal plants

Plant-antivenom is a computational Websystem about medicinal plants with anti-venom properties. The system consists of a database of these plants, including scientific publications on this subject and amino acid sequences of active principles from venomous animals. The system relates these data allowing their integration through different search applications. For the development of the system, the first surveys were conducted in scientific literature, allowing the creation of a publication database in a library for reading and user interaction. Then, classes of categories were created, allowing the use of tags and the organization of content. This database on medicinal plants has information such as family, species, isolated compounds, activity, inhibited animal venoms, among others. Provision is made for submission of new information by registered users, by the use of wiki tools. Content submitted is released in accordance to permission rules defined by the system. The database on biological venom protein amino acid sequences was structured from the essential information from National Center for Biotechnology Information (NCBI). Plant-antivenom's interface is simple, contributing to a fast and functional access to the system and the integration of different data registered on it. Plant-antivenom system is available on the Internet at http://gbi.fmrp.usp.br/plantantivenom

Detection of differentially methylated regions of irradiated fig tree selections

Fig tree (Ficus carica L.) breeding programs using conventional methods, such as directed crosses, to obtain new cultivars, are unworkable in many countries, including Brazil. Consequently, genetic breeding through mutagenesis has emerged as an important line of research that can improve this crop, and be a significant source of information about this species and assist in the implementation of propagation projects and appropriate management. The aim of this study was to verify the existence of epigenetic variability attributable to DNA methylation in irradiated fig selections when compared both to each other and to the main commercial cultivar, “Roxo-de-Valinhos”, which had previously used methylation-sensitive amplified polymorphism (MSAP) and DNA sequencing to detect the position of polymorphic regions, analyzable by bioinformatic tools. The sequencing of DNA, isolated from the differentially methylated sites, makes it possible to observe different patterns of methylation by sequencing the treated DNA with sodium bisulfite in the coding regions of regulatory genes active in the development, and fruit ripening stages. Furthermore, they have been found in the mitochondrial DNA of treatments which regulate the supply of energy in Adenosine triphosphate (ATP) form in plants. Closely related to their development, they justify the different phenotypes found in both fruit and plant growth that have suffered stress due to exposure to gamma radiation. Thus, future studies on gene expression in treatments have emerged as an extremely important strategy for understanding these complex regulatory systems, which may lead to the identification of genes of agricultural interest for the fig tree crop, and allow for manipulation and subsequent propagation of improved crops for commercial purposes

Understanding the Role of Intrinsic Disorder of Viral Proteins in the Oncogenicity of Different Types of HPV

Intrinsic disorder is very important in the biological function of several proteins, and is directly linked to their foldability during interaction with their targets. There is a close relationship between the intrinsically disordered proteins and the process of carcinogenesis involving viral pathogens. Among these pathogens, we have highlighted the human papillomavirus (HPV) in this study. HPV is currently among the most common sexually transmitted infections, besides being the cause of several types of cancer. HPVs are divided into two groups, called high- and low-risk, based on their oncogenic potential. The high-risk HPV E6 protein has been the target of much research, in seeking treatments against HPV, due to its direct involvement in the process of cell cycle control. To understand the role of intrinsic disorder of the viral proteins in the oncogenic potential of different HPV types, the structural characteristics of intrinsically disordered regions of high and low-risk HPV E6 proteins were analyzed. In silico analyses of primary sequences, prediction of tertiary structures, and analyses of molecular dynamics allowed the observation of the behavior of such disordered regions in these proteins, thereby proving a direct relationship of structural variation with the degree of oncogenicity of HPVs. The results obtained may contribute to the development of new therapies, targeting the E6 oncoprotein, for the treatment of HPV-associated diseases

Modeling the pHLA/TCR Complex in a Lipid Bilayer Environment

<p>Multiple sclerosis (MS) is mediated by T cell responses to antigens of the central nervous system, such as myelin basic protein (MBP). The Human Leucocyte Antigen (HLA) locus is the main region associated with the disease, where certain alleles of the DRB1 gene have been linked to both predisposition and protection against MS. The binding groove of the HLA-DR heterodimer interacts with specific peptides, while T-cell receptor (TCR) recognize the complex formed by the peptide and HLA (pHLA). Understanding the preferences of this interaction may help understand susceptibility to MS. Although X-ray crystallography has been employed to determine the structure of pHLA/TCR, it does not encompass the transmembrane regions. Therefore, the aim of this study was to model the pHLA/TCR complex within a membrane environment to evaluate its stability and dynamic behavior. The complete model of this complex was generated using the MODELLER program. Atomic coordinates from the pHLA/TCR crystal (PDB ID: 1YMM) were extracted and used as the initial model, with structural gaps filled using models available in the Alphafold Protein Structure Database. A loop refinement algorithm was employed to adjust the positions of the binding, transmembrane, and cytoplasmic regions, which were oriented along the z-axis, while geometric constraints were imposed to preserve the integrity of the transmembrane helices. A heterogeneous lipid bilayer was constructed via the CHARMM-GUI server, and subsequently, the modeled complex was manually inserted into two lipid bilayers using VMD software. A 50 ns molecular dynamics (MD) simulation was conducted using the GROMACS program. The best model resulting of pHLA/TCR exhibited helices aligned parallel to the z-axis, enabling their insertion into lipid bilayers, followed by MD simulations. The resulting trajectories demonstrated that the system achieved stability throughout the simulated period, maintaining the complete integrity of the pHLA-TCR interaction. This suggests that the model is suitable for further investigations into this complex interaction in membranous environments. To analyze the potential influence of DRB1 gene polymorphisms on MS susceptibility, the next steps of this research involve modeling pHLA-DR complexes corresponding to different alleles and comparing their interactions with specific TCRs and peptides.</p&gt

Investigating SARS-CoV-2 Spike Glycoprotein: Insights from Molecular Modeling and Dynamics Simulationson Wild-Type and Variants Interactions with ACE2 and Furin

<p>The binding affinity between the Spike (S) glycoprotein and its host cell receptors, angiotensin-converting enzyme 2 (ACE2) and Furin plays a critical role in determining SARS-CoV-2 replication rates. Variants of the S protein, including Alpha, Beta, Gamma, Delta, Omicron BA.1, BA.2, BA.4, and BA.5, have been associated with shifting levels of COVID-19 susceptibility and severity. However, the mechanisms underlying these virus-host protein interactions are not fully understood. The current research employs molecular modeling, protein-protein interaction, and molecular dynamics (MD) simulations of Wild-Type (WT) and variants of virus-host complexes ACE2-Spike-Furin to investigate interactions and stability. The objective is to gain a comprehensive understanding of protein complex dynamics and their relevance to COVID-19. Protein 3D structures were obtained from the Protein Data Bank, while MODELLER was employed to model S protein variants. Glycans were incorporated using the Glycan Reader & Modeller tool. Complexes were chosen based on HADDOCK scores, with lower scores signifying greater reliability. Interaction free energies were calculated using the PRODIGY server. MD simulations were conducted using GROMACS version 2019.3 with the CHARMM36 force field. The complexes were solvated, neutralized, minimized, and equilibrated under an NVT and NPT ensemble. The production phase was performed at 300K for 100ns. Complex selection was based on both the lowest HADDOCK scores and the free energies of each interaction. ACE2-Spike interactions displayed binding affinities ranging from -11.4 to -15.1 kcal/mol for WT Spike and its variants. Spike-Furin interactions exhibited affinities ranging from -10.5 to -12.6 kcal/mol. 28 glycans were incorporated into each complex. Throughout the MD simulations, all complexes demonstrated stability, as corroborated by RMSD, RMSF, Gyration, and SASA analyses, though with specific variations related to each variant. This project uniquely explores the interactions among three proteins and glycans, yielding high-fidelity complex models. These findings are an integral component of a comprehensive analysis that will additionally investigate the interactions of the TMPRSS2 protein and employ machine learning techniques to discern differences among SARS-CoV-2 lineages, aiming to understand genetic variations and gain insights into S protein dynamics, thereby enhancing our comprehension of SARS-CoV-2's protein-protein biology.</p&gt

Structural Characterization of the Interaction of Hypoxia Inducible Factor-1 with Its Hypoxia Responsive Element at the −964G > A Variation Site of the <i>HLA-G</i> Promoter Region

Human Antigen Leukocyte-G (HLA-G) gene encodes an immune checkpoint molecule that has restricted tissue expression in physiological conditions; however, the gene may be induced in hypoxic conditions by the interaction with the hypoxia inducible factor-1 (HIF1). Hypoxia regulatory elements (HRE) located at the HLA-G promoter region and at exon 2 are the major HIF1 target sites. Since the G allele of the −964G > A transversion induces higher HLA-G expression when compared to the A allele in hypoxic conditions, here we analyzed HIF1-HRE complex interaction at the pair-atom level considering both −964G > A polymorphism alleles. Mouse HIF2 dimer crystal (Protein Data Bank ID: 4ZPK) was used as template to perform homology modelling of human HIF1 quaternary structure using MODELLER v9.14. Two 3D DNA structures were built from 5′GCRTG’3 HRE sequence containing the −964G/A alleles using x3DNA. Protein-DNA docking was performed using the HADDOCK v2.4 server, and non-covalent bonds were computed by DNAproDB server. Molecular dynamic simulation was carried out per 200 ns, using Gromacs v.2019. HIF1 binding in the HRE containing −964G allele results in more hydrogen bonds and van der Waals contact formation than HRE with −964A allele. Protein-DNA complex trajectory analysis revealed that HIF1-HRE-964G complex is more stable. In conclusion, HIF1 binds in a more stable and specific manner at the HRE with G allele

Plant-antivenom: Database of anti-venom medicinal plants

Plant-antivenom is a computational Websystem about medicinal plants with anti-venom properties. The system consists of a database of these plants, including scientific publications on this subject and amino acid sequences of active principles from venomous animals. The system relates these data allowing their integration through different search applications. For the development of the system, the first surveys were conducted in scientific literature, allowing the creation of a publication database in a library for reading and user interaction. Then, classes of categories were created, allowing the use of tags and the organization of content. This database on medicinal plants has information such as family, species, isolated compounds, activity, inhibited animal venoms, among others. Provision is made for submission of new information by registered users, by the use of wiki tools. Content submitted is released in accordance to permission rules defined by the system. The database on biological venom protein amino acid sequences was structured from the essential information from National Center for Biotechnology Information (NCBI). Plant-antivenom`s interface is simple, contributing to a fast and functional access to the system and the integration of different data registered on it. Plant-antivenom system is available on the Internet at http://gbi.fmrp.usp.br/plantantivenom.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES