Biology subjects

Velez Rueda, A. J.

Publications and source records attributed to Velez Rueda, A. J..

5 recordsLinked to original sources

bioRxiv2022

CaviDB: a database of cavities and their features in the structural and conformational space of proteins

Proteins are the functional and evolutionary units of cells. On their surface, proteins are sculpted into numerous concavities and bulges, offering unique microenvironments for ligand binding or catalysis. The dynamics, size, and chemical features of these cavities are essential for the mechanistic understanding of protein function. Here we present CaviDB (https://www.cavidb.org), a novel database of cavities and their features in known protein structures, which integrates the results from commonly used software for cavities detection with protein features obtained from sequence, structure, and function analyses. Additionally, each protein in CaviDB is associated with its corresponding conformers which help to analyze conformational changes in cavities as well. We were able to characterize a total number of 16,533,339 cavities, 62,0431 of them predicted as druggable targets. CaviDB contains 276,432 different proteins, with information about all their conformers. It also offers the capability to compare cavities and their features from different conformational states of the protein. Furthermore, we have recently added the available models from the AlphaFold database versions 2 and 3, which allow further cavity explorations and comparisons. Each entry information is organized in sections, highlighting the general cavities descriptors, including the inter-cavities contacts, activated residues per cavity, the information about druggable cavities, and the global protein descriptors. The data retrieved by the user can be downloaded in a format that is easy to parse and integrate with custom pipelines for protein analysis. CaviDB aims to offer a comprehensive database for use not only in different aspects of drug design and discovery but also to better understand the basis of the protein structure-function relationship better. With its unique approach, CaviDB provides an essential resource for the wide community of bioinformaticians in particular and biologists in general.

bioinformatics↗

bioRxiv2021

Impact of protein conformational diversity on AlphaFold predictions

After the outstanding breakthrough of AlphaFold in predicting protein 3D models, new questions appeared and remain unanswered. The ensemble nature of proteins, for example, challenges the structural prediction methods because the models should represent a set of conformers instead of single structures. The evolutionary and structural features captured by effective deep learning techniques may unveil the information to generate several diverse conformations from a single sequence. Here we address the performance of AlphaFold2 predictions under this ensemble paradigm. Using a curated collection of apo-holo conformations, we found that AlphaFold2 predicts the holo form of a protein in 70% of the cases, being unable to reproduce the observed conformational diversity with an equivalent error than in the estimation of a single conformation. More importantly, we found that AlphaFold2s performance worsens with the increasing conformational diversity of the studied protein. This impairment is related to the heterogeneity in the degree of conformational diversity found between different members of the homologous family of the protein under study. Finally, we found that main-chain flexibility associated with apo-holo pairs of conformers negatively correlates with the predicted local model quality score plDDT, indicating that plDDT values in a single 3D model could be used to infer local conformational changes linked to ligand binding transitions.

bioinformatics↗

bioRxiv2021

CardIAP: Calcium images analyzer web application

MotivationIonic calcium (Ca2+) plays the role of the second messenger in eukaryotic cells associated with cellular functions of regulation of the cell cycle, such as transport, motility, gene expression, and metabolism (Permyakov and Kretsinger, 2009). The use of fluorometric techniques in isolated cells, loaded with Ca2+ sensitive fluorescent probes allows the quantitative measurement of dynamic events that occur in living, functioning cells. The Cardiomyocytes Images Analyzer Application (CardIAP) covers the need for tools to analyze and retrieve information from confocal microscopy images, in a systematic, accurate, and fast way. ResultsHere we present the CardIAP web app, an automated method for the identification of spatio-temporal patterns in a calcium fluorescence imaging sequence. Through this tool, users can analyze single or multiple Ca2+ transients from confocal line-scan images and obtain quantitative information on the dynamic response of the stimulated myocyte. Our web application also allows the user the extraction of data on calcium dynamics in downloadable tables and plots, simplifying the calculation of the alternation and discordance indices and their classification. CardIAP could assist in studying the underlying mechanisms of anomalous calcium release phenomena. Availability and implementationCardIAP is an open-source app, entirely developed in Python, which can be freely accessed and used at http://cardiap.herokuapp.com/.

bioinformatics↗

bioRxiv2021

Structural and evolutionary analysis unveil functional adaptations in the promiscuous behavior of serum albumins

Promiscuous activities have been related to the capacity to catalyze reactions different from those a protein has evolved to sustain. From this evolutionary perspective, we rethought the serum albumins promiscuous behavior. We found that the cross aldol condensation of acetone and p-formylbenzonitrile is a promiscuous reaction conserved in humans and other mammals. Structural and evolutionary analysis indicates that the involved residues could have evolved for a still unknown biological function. Our results could contribute to better characterize the serum albumin family and raise questions about the evolution of protein promiscuity and function.

bioinformatics↗

bioRxiv2018

ProtMiscuity: a database of promiscuous proteins

SummaryProtMiscuity is a manually-curated database of promiscuous proteins. It is annotated with information about canonical and promiscuous activities comprising 88 different reactions in 57 proteins from 40 organisms. ProtMiscuity could assist in the study of the underlying mechanisms of promiscuous reactions by offering a collection of experimentally derived data, extensively linked with other databases providing biological, structural and functional information.\n\nAvailability and ImplementationThe responsive web interface of ProtMiscuity provides support for easier navigation and visualization of the database contents on multiple devices. It is implemented in HTML, CSS, JavaScript, Angular4 and NodeJS. ProtMiscuity is hosted on our server and can be freely accessed at http://ufq.unq.edu.ar/protmiscuity\n\nContactGustavo Parisi (gustavo@unq.edu.ar)

bioinformatics↗