Unlocking Precision Docking for Metalloproteins.

Metalloproteins play a fundamental role in molecular biology, contributing to various biological processes. However, the discovery of high-affinity ligands targeting metalloproteins has been delayed due, in part, to a lack of suitable tools and data. Molecular docking, a widely used technique for virtual screening of small-molecule ligand interactions with proteins, often faces challenges when applied to metalloproteins due to the particular nature of the ligand metal bond. To address these limitations associated with docking metalloproteins, we introduce a knowledge-driven docking approach known as "metalloprotein bias docking" (MBD), which extends the AutoDock Bias technique. We assembled a comprehensive data set of metalloprotein-ligand complexes from 15 different metalloprotein families, encompassing Ca, Co, Fe, Mg, Mn, and Zn metal ions. Subsequently, we conducted a performance analysis of our MBD method and compared it to the conventional docking (CD) program AutoDock4, applied to various metalloprotein targets within our data set. Our results demonstrate that MBD outperforms CD, significantly enhancing accuracy, selectivity, and precision in ligand pose prediction. Additionally, we observed a positive correlation between our predicted ligand free energies and the corresponding experimental values. These findings underscore the potential of MBD as a valuable tool for the effective exploration of metalloprotein-ligand interactions.

Climatic adaptation and ecological descriptors of wild beans from Mexico.

Despite its economic, social, biological, and cultural importance, wild forms of the genus Phaseolus are not well represented in germplasm banks, and they are at great risk due to changes in land use as well as climate change. To improve our understanding of the potential geographical distribution of wild beans (Phaseolus spp.) from Mexico and support in situ and ex situ conservation programs, we determined the climatic adaptation ranges of 29 species and two subspecies of Phaseolus collected throughout Mexico. Based on five biotic and 117 abiotic variables obtained from different databases-WorldClim, Global-Aridity, and Global-PET-we performed principal component and cluster analyses. Germplasm was distributed among 12 climatic types from a possible 28. The general climatic ranges were as follows: 8-3,083 m above sea level; 12.07-26.96°C annual mean temperature; 10.33-202.68 mm annual precipitation; 9.33-16.56 W/m2 of net radiation; 11.68-14.23 hr photoperiod; 0.06-1.57 aridity index; and 10-1,728 mm/month of annual potential evapotranspiration. Most descriptive variables (25) clustered species into two groups: One included germplasm from semihot climates, and the other included germplasm from temperate climates. Species clustering showed 45% to 54% coincidence with species previously grouped using molecular data. The species P. filiformis, P. purpusii, and P. maculatus were found at low-humidity locations; these species could be used to improve our understanding of the extreme aridity adaptation mechanisms used by wild beans to avoid or tolerate climate change as well as to introgress favorable alleles into new cultivars adapted to hot, dry environments.

Analysis of mitochondrial genetic diversity of Ustilago maydis in Mexico.

The current understanding of the genetic diversity of the phytopathogenic fungus Ustilago maydis is limited. To determine the genetic diversity and structure of U. maydis, 48 fungal isolates were analyzed using mitochondrial simple sequence repeats (SSRs). Tumours (corn smut or 'huitlacoche') were collected from different Mexican states with diverse environmental conditions. Using bioinformatic tools, five microsatellites were identified within intergenic regions of the U. maydis mitochondrial genome. SSRMUM4 was the most polymorphic marker. The most common repeats were hexanucleotides. A total of 12 allelic variants were identified, with a mean of 2.4 alleles per locus. An estimate of the genetic diversity using analysis of molecular variance (AMOVA) revealed that the highest variance component is within states (84%), with moderate genetic differentiation between states (16%) (FST = 0.158). A dendrogram generated using the unweighted paired-grouping method with arithmetic averages (UPGMA) and the Bayesian analysis of population structure grouped the U. maydis isolates into two subgroups (K = 2) based on their shared SSRs.

Insights from the genome of the biotrophic fungal plant pathogen Ustilago maydis.

Ustilago maydis is a ubiquitous pathogen of maize and a well-established model organism for the study of plant-microbe interactions. This basidiomycete fungus does not use aggressive virulence strategies to kill its host. U. maydis belongs to the group of biotrophic parasites (the smuts) that depend on living tissue for proliferation and development. Here we report the genome sequence for a member of this economically important group of biotrophic fungi. The 20.5-million-base U. maydis genome assembly contains 6,902 predicted protein-encoding genes and lacks pathogenicity signatures found in the genomes of aggressive pathogenic fungi, for example a battery of cell-wall-degrading enzymes. However, we detected unexpected genomic features responsible for the pathogenicity of this organism. Specifically, we found 12 clusters of genes encoding small secreted proteins with unknown function. A significant fraction of these genes exists in small gene families. Expression analysis showed that most of the genes contained in these clusters are regulated together and induced in infected tissue. Deletion of individual clusters altered the virulence of U. maydis in five cases, ranging from a complete lack of symptoms to hypervirulence. Despite years of research into the mechanism of pathogenicity in U. maydis, no 'true' virulence factors had been previously identified. Thus, the discovery of the secreted protein gene clusters and the functional demonstration of their decisive role in the infection process illuminate previously unknown mechanisms of pathogenicity operating in biotrophic fungi. Genomic analysis is, similarly, likely to open up new avenues for the discovery of virulence determinants in other pathogens.

Factores de riesgo asociados con la hipertensión arterial en los trabajadores de la oficina central del MINBAS

Se realizó un estudio descriptivo del total de hipertensos que laboran en el Ministerio de la Industria Básica, en el período de enero a diciembre de 1995 con el objetivo de identificar los factores de riesgo que favorezcan la aparición de la hipertensión arterial y sus diferencias según el sexo. El grupo de edad más afectado fue el comprendido entre 50 y 59 añoos, con predominio del sexo masculino. La historia familiar de hipertensión arterial (96,5 porciento), la cardiopatía isquémica (32,60 porciento) y la hipercolesterolemia (30,60 porciento), estuvo presente aunque su relación con el sexo no fue significativa. La hipertensión arterial se vio relacionada de forma significativa con la obesidad en el sexo femenino y con el hábito de fumar, el sedentarismo y la categoría ocupacional de dirigente en el sexo masculino

Factores de riesgo asociados con la hipertensión arterial en los trabajadores de la oficina central del MINBAS

Se realizó un estudio descriptivo del total de hipertensos que laboran en el Ministerio de la Industria Básica, en el período de enero a diciembre de 1995 con el objetivo de identificar los factores de riesgo que favorezcan la aparición de la hipertensión arterial y sus diferencias según el sexo. El grupo de edad más afectado fue el comprendido entre 50 y 59 añoos, con predominio del sexo masculino. La historia familiar de hipertensión arterial (96,5 porciento), la cardiopatía isquémica (32,60 porciento) y la hipercolesterolemia (30,60 porciento), estuvo presente aunque su relación con el sexo no fue significativa. La hipertensión arterial se vio relacionada de forma significativa con la obesidad en el sexo femenino y con el hábito de fumar, el sedentarismo y la categoría ocupacional de dirigente en el sexo masculino (AU)