Generating protein folding trajectories using contact-map-driven directed walks

Recent advances in machine learning methods have had a significant impact on protein structure prediction, but accurate generation and characterization of protein-folding pathways remains intractable. Here, we demonstrate how protein folding trajectories can be generated using a directed walk strategy operating in the space defined by the residue-level contact-map. This double-ended strategy views protein folding as a series of discrete transitions between connected minima on the potential energy surface. Subsequent reaction-path analysis for each transition enables thermodynamic and kinetic characterization of each protein-folding path. We validate the protein-folding paths generated by our discretized-walk strategy against direct molecular dynamics simulations for a series of model coarse-grained proteins constructed from hydrophobic and polar residues. This comparison demonstrates that ranking discretized paths based on the intermediate energy barriers provides a convenient route to identifying physically sensible folding ensembles. Importantly, by using directed walks in the protein contact-map space, we circumvent several of the traditional challenges associated with protein-folding studies, namely, long time scales required and the choice of a specific order parameter to drive the folding process. As such, our approach offers a useful new route for studying the protein-folding problem

Combined effect of age and body mass index on postoperative mortality and morbidity in laparoscopic cholecystectomy patients

BackgroundPrevious studies have assessed the impact of age and body mass index (BMI) on surgery outcomes separately. This retrospective cohort study aimed to investigate the combined effect of age and BMI on postoperative mortality and morbidity in patients undergoing laparoscopic cholecystectomy.MethodsData from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database for laparoscopic cholecystectomy patients between 2008 and 2020 were analyzed. Patient demographics, functional status, admission sources, preoperative risk factors, laboratory data, perioperative variables, and 30-day postoperative outcomes were included in the dataset. Logistic regression was used to determine the association of age, BMI, and age/BMI with mortality and morbidity. Patients were stratified into different subcategories based on their age and BMI, and the age/BMI score was calculated. The chi-square test, independent sample t-test, and ANOVA were used as appropriate for each category.ResultsThe study included 435,052 laparoscopic cholecystectomy patients. Logistic regression analysis revealed that a higher age/BMI score was associated with an increased risk of mortality (adj OR 13.13 95% CI, 9.19–18.77, p < 0.0001) and composite morbidity (adj OR 2.57, 95% CI 2.23–2.95, p < 0.0001).ConclusionOlder age, especially accompanied by a low BMI, appears to increase the post-operative mortality and morbidity risks in laparoscopic cholecystectomy patients, while paradoxically, a higher BMI seems to be protective. Our hypothesis is that a lower BMI, perhaps secondary to malnutrition, can carry a greater risk of surgery complications for the elderly. Age/BMI is strongly and positively associated with mortality and morbidity and could be used as a new scoring system for predicting outcomes in patients undergoing surgery. Nevertheless, laparoscopic cholecystectomy remains a very safe procedure with relatively low complication rates

Dataset for "Generating protein folding trajectories using contact-map-driven directed walks"

Recent advances in machine learning methods have had a significant impact on protein structure prediction, but accurate generation and characterization of protein-folding pathways remains intractable. Here, we demonstrate how protein folding trajectories can be generated using a directed walk strategy operating in the space defined by the residue-level contact-map. This double-ended strategy views protein folding as a series of discrete transitions between connected minima on the potential energy surface. Subsequent reaction-path analysis for each transition enables thermodynamic and kinetic characterization of each protein-folding path. We validate the protein-folding paths generated by our discretized-walk strategy against direct molecular dynamics simulations for a series of model coarse-grained proteins constructed from hydrophobic and polar residues. This comparison demonstrates that ranking discretized paths based on the intermediate energy barriers provides a convenient route to generating physically-sensible folding ensembles. Importantly, by using directed walks in the protein contact-map space, we circumvent several of the traditional challenges associated with protein-folding studies, namely long time-scales required and unknown order parameters. As such, our approach offers a useful new route for studying the protein-folding problem

Eat, sleep, code, repeat : tips for early-career researchers in computational science

This article is intended as a guide for new graduate students entering the field of computational science. With the increasing influx of students with diverse backgrounds joining the ever-popular field, the aim of this short guide is to help students navigate through the various computational techniques that they are likely to encounter during their studies. Here, we cover a broad spectrum of techniques, including Bash scripting, scientific programming, and machine learning, among other fields. This paper is structured into nine sections, each introducing a different computational method. To enhance readability, we have adopted a casual and instructive tone throughout and included relevant code snippets. Please note that due to the introductory nature of this article, it is not intended to be exhaustive; instead, we direct readers to a list of references to expand their knowledge of the techniques discussed within the paper. Finally, readers should note this article serves as an extension to our student-led seminar series, with additional resources and videos available at https://computationaltoolkit.github.io/ for reference

Associations of Free, Bioavailable, and Total 25-Hydroxyvitamin D with Neonatal Birth Anthropometry and Calcium Homeostasis in Mother-Child Pairs in a Sunny Mediterranean Region.

Sufficient vitamin D status is crucial for successful pregnancy and fetal development. The assessment of 25-hydroxyvitamin D [25(OH)D] concentrations is commonly used to evaluate vitamin D status. Additionally, bioavailable 25(OH)D, encompassing both free and albumin-bound fractions, is considered significant for pregnancy-related outcomes. However, limited research has been conducted on the correlation between free and bioavailable 25(OH)D concentrations and neonatal parameters.Our objective was to examine the interrelated biodynamics of maternal and neonatal total, free, and bioavailable 25(OH)D in maternal-neonatal dyads at birth, and their associations with homeostasis and neonatal birth anthropometry.We analyzed a cohort of 70 full-term mother-child pairs. At birth, we evaluated maternal and neonatal concentrations of total, free, and bioavailable 25(OH)D, as well as calcium and parathyroid hormone concentrations. Additionally, we assessed neonatal anthropometric profiles, including birth weight, head circumference, chest circumference, and abdomen circumference.We found positive associationsbetween all neonatal measures of vitamin D status [total - free 25(OH)D: beta coefficient (β) 6.10 (95% CI, 4.92,7.28)], total-bioavailable 25(OH)D: 6.48 (95% CI, 4.92,8.04)]. Maternal forms exhibited a similar patternof association, except for the bioavailable maternal form. In multivariate analysis, both total and free maternal 25(OH)D concentrations were correlated with all neonatal forms [neonatal total 25(OH)D: 1.29 (95% CI, 1.12,1.46) for maternal total 25(OH)D, 10.89 (8.16,13.63) for maternal free 25(OH)D], [neonatal free 25(OH)D: 0.15 for maternal total 25(OH)D, 1.28 (95% CI, 0.89,1.68) for maternal free 25(OH)D], and [0.13 (95% CI, 0.10, 0.16), 1.06 (95% CI, 0.68,1.43) for maternal free 25(OH)D], respectively, with the exclusion of the bioavailable maternal form.We observed no significant interactions within or between groups regarding maternal and neonatal vitamin D parameters and maternal calcium and parathyroid hormone concentrations, except for a borderline association between neonatal bioavailable 25(OH)D and albumin-adjusted neonatal calcium concentrations. Additionally, we found no significant association between maternal-neonatal vitamin D forms and neonatal birth anthropometry.Our study indicates that bioavailable maternal and neonatal 25(OH)D have no significant effects on vitamin D equilibrium, calcium homeostasis, and neonatal anthropometry at birth. However, we observed a remarkable biodynamic interaction between maternal and neonatal total and free 25(OH)D concentrations at the maternal-neonatal interface, with no associations observed with other calciotropic or anthropometric outcomes