A5075863884- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Evolution and Genetic Dynamics
- Machine Learning in Bioinformatics
- Genomics and Phylogenetic Studies
- Trace Elements in Health
- Gene expression and cancer classification
- Bioinformatics and Genomic Networks
- Genetics, Bioinformatics, and Biomedical Research
- Enzyme Structure and Function
- Ubiquitin and proteasome pathways
- Plant nutrient uptake and metabolism
- Plant Stress Responses and Tolerance
- Plant Micronutrient Interactions and Effects
- Protein Degradation and Inhibitors
- Genomics and Rare Diseases
- Evolutionary Game Theory and Cooperation
- Epigenetics and DNA Methylation
- Microbial Metabolic Engineering and Bioproduction
- Advanced Proteomics Techniques and Applications
- Cellular Automata and Applications
- Coral and Marine Ecosystems Studies
- Photosynthetic Processes and Mechanisms
- Animal Ecology and Behavior Studies
- Alzheimer's disease research and treatments
CeMM Research Center for Molecular Medicine
2022-2025
Austrian Academy of Sciences
2022-2025
University of Valparaíso
2025
Complex Engineering System Institute
2021-2025
Valparaiso University
2025
University of Vienna
2023
Universidad Mayor
2018-2019
University of Washington
2017
Santa Fe Institute
2013-2014
University of Zurich
2008-2012
Chemical modulation of proteins enables a mechanistic understanding biology and represents the foundation most therapeutics. However, despite decades research, 80% human proteome lacks functional ligands. proteomics has advanced fragment-based ligand discovery toward cellular systems, but throughput limitations have stymied scalable identification fragment-protein interactions. We report proteome-wide maps protein-binding propensity for 407 structurally diverse small-molecule fragments....
Abstract The human solute carrier (SLC) superfamily of ~460 membrane transporters remains the largest understudied protein family despite its therapeutic potential. To advance SLC research, we developed a comprehensive knowledgebase that integrates systematic multi-omics data sets with selected curated information from public sources. We annotated substrates through literature curation, compiled disease associations using mining techniques, and determined subcellular localization SLCs by...
Abstract Background As in many different areas of science and technology, most important problems bioinformatics rely on the proper development assessment binary classifiers. A generalized performance classifiers is typically carried out through analysis their receiver operating characteristic (ROC) curves. The area under ROC curve (AUC) constitutes a popular indicator classifier. However, statistical significance difference between any two based this measure not straightforward task, since...
Prokaryotic genomes are small and compact. Either this feature is caused by neutral evolution or natural selection favoring genomes-genome streamlining. Three separate prior lines of evidence argue against streamlining for most prokaryotes. We find that the same three in thermophile bacteria. Specifically, with increasing habitat temperature decreasing genome size, proportion genomic DNA intergenic regions decreases. Furthermore, temperature, generation time Genome-wide selective constraints...
Solute carriers are an operationally defined diverse family of membrane proteins involved in the transport nutrients, metabolites, xenobiotics, and drugs. Here, we provide integrative classification solute by combining evolutionary information with proteome-wide structure models recently made available through AlphaFold resource. Analyses orthologous relations among 455 protein-coding genes currently classified as human carriers, over fully sequenced genomes 2,100 species, suggest no more...
Recent laboratory experiments suggest that a molecule's ability to evolve neutrally is important for its generate evolutionary innovations. In contrast experiments, life unfolds on time-scales of billions years. Here, we ask whether neutrally-a measure robustness-facilitates innovation also these large time-scales. To this end, use protein designability, the number sequences can adopt given structure, as an estimate structure's neutrally. Based two complementary measures functional...
Molecular glue degraders (MGDs) are small molecules that degrade proteins of interest via the ubiquitin–proteasome system. While MGDs were historically discovered serendipitously, approaches for MGD discovery now include cell-viability-based drug screens or data mining public transcriptomics and response datasets. These approaches, however, have target spaces restricted to essential proteins. Here we develop a high-throughput workflow also reaches nonessential proteome. This begins with...
The organization of protein structures in genotype space is well studied. same does not hold for functions, whose important to understand how novel functions can arise through blind evolutionary searches sequence space. In systems other than proteins, two organizational features facilitate phenotypic innovation. first that genotypes with the phenotype form vast and connected networks. second different neighborhoods this contain phenotypes. We here characterize enzymatic space, using a data...
Abstract Research on the understudied solute carrier (SLC) superfamily of membrane transporters would greatly profit from a comprehensive knowledgebase, synthesizing data and knowledge different aspects SLC function. We consolidated multi-omics sets with selected curated information public domain, such as structure prediction, substrate annotation, disease association subcellular localization. This SLC-centric is made accessible to scientific community via web portal, featuring interactive...
<title>Abstract</title> Recent studies suggest that the human circadian clock influences periodic changes in composition of gut microbiota, which is essential for maintaining host health. This connection has led researchers to hypothesize disruption may impact health via microbiota. Here, we rhythmic bacteria—those whose abundance fluctuates a pattern—are key drivers differences microbiota between healthy individuals and those with circadian-related diseases. Even absence causal relation,...
The human SLC39A8 ( hSLC39A8 ) gene encodes a plasma membrane protein (ZIP8) that mediates the specific uptake of metals Cd 2+ , Mn Zn Fe Co and Se 4+ . Pathogenic variants within are associated with congenital disorder glycosylation type 2 (CDG II) or Leigh-like syndrome. However, numerous mutations uncertain significance also linked to different conditions benign traits. Our study characterized 21 measured their impact on localization intracellular levels We identified four disrupt...
Creatine is an essential metabolite for the storage and rapid supply of energy in muscle nerve cells. In humans, impaired metabolism, transport, distribution creatine throughout tissues can cause varying forms mental disability, also known as deficiency syndrome (CDS). So far, 80 mutations transporter (SLC6A8) have been associated to CDS. To better understand effect human genetic variants on physiology SLC6A8 their possible impact CDS, we studied 30 missense including 15 unknown...
Predict SLC6 mutation clinical pathogenicity by calculating the amino acid descriptors in different ranges with rationalization analysis of prediction.
Empirical or knowledge-based potentials have many applications in structural biology such as the prediction of protein structure, protein-protein, and protein-ligand interactions evaluation stability for mutant proteins, assessment errors experimentally solved structures, design new proteins. Here, we describe a simple procedure to derive use pairwise distance-dependent that rely on definition effective atomic interactions, which attempt capture are more likely be physically relevant. Based...
The accurate assessment of structural errors plays a key role in protein structure prediction, constitutes the first step refinement, and has major impact on subsequent functional inference from data. In this study, we assess compare ability different full atom knowledge-based potentials to detect small localized comparative models known accuracy. We have evaluated effect incorporating close nonbonded pairwise terms task classifying residue modeling Since direct unbiased derivation current...
An essential aspect of the current theory adaptive speciation is maintenance phenotypic variation and evolution stationary stable diversity, a phenomenon known as evolutionary branching. Theoretical empirical evidence suggest that can be maintained by favoring rare phenotypes, for example, through frequency-dependent selection. However, even when provided, conditions leading to branching are not universal. In order lead diversification, models speciation, such Lotka-Volterra competition...