BioSimulators: a central registry of simulation engines and services for recommending specific tools.

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations.

SAR of non-hydrolysable analogs of pyridoxal 5'-phosphate against low molecular weight protein tyrosine phosphatase isoforms.

Kinases and phosphatases are key enzymes in cell signal transduction pathways. Imbalances in these enzymes have been linked to numerous disease states ranging from cancer to diabetes to autoimmune disorders. The two isoforms (IFA and IFB) of Low Molecular Weight Protein Tyrosine Phosphatase (LMW-PTP) appear to play a role in these diseases. Pyridoxal 5'-phosphate (PLP) has been shown to act as a potent but, impractical micromolar inhibitor for both isoforms. In this study, a series of non-hydrolysable phosphonate analogs of PLP were designed, synthesized and tested against the two isoforms of LMW-PTP. Assay results demonstrated that the best inhibitor for both isoforms was compound 5 with a Kis of 1.84 µM (IFA) and 15.6 µM (IFB). The most selective inhibitor was compound 16, with a selectivity of roughly 370-fold for IFA over IFB.

Use of interactive mathematical simulations in Fundamentals of Biochemistry, a LibreText online educational resource, to promote understanding of dynamic reactions.

Biology is perhaps the most complex of the sciences, given the incredible variety of chemical species that are interconnected in spatial and temporal pathways that are daunting to understand. Their interconnections lead to emergent properties such as memory, consciousness, and recognition of self and non-self. To understand how these interconnected reactions lead to cellular life characterized by activation, inhibition, regulation, homeostasis, and adaptation, computational analyses and simulations are essential, a fact recognized by the biological communities. At the same time, students struggle to understand and apply binding and kinetic analyses for the simplest reactions such as the irreversible first-order conversion of a single reactant to a product. This likely results from cognitive difficulties in combining structural, chemical, mathematical, and textual descriptions of binding and catalytic reactions. To help students better understand dynamic reactions and their analyses, we have introduced two kinds of interactive graphs and simulations into the online educational resource, Fundamentals of Biochemistry, a LibreText biochemistry book. One is available for simple binding and kinetic reactions. The other displays progress curves (concentrations vs. time) for simple reactions and complex metabolic and signal transduction pathways. Users can move sliders to change dissociation and kinetic constants as well as initial concentrations and see instantaneous changes in the graphs. They can also export data into a spreadsheet for further processing, such as producing derivative Lineweaver-Burk and traditional Michaelis-Menten graphs of initial velocity (v0) versus substrate concentration.

Identification of new inhibitors for low molecular weight protein tyrosine phosphatase isoform B.

The National Cancer Institute Diversity Set II (1356 compounds) and Diversity Set III (1597 compounds) were screened via in silico methods as potential inhibitors of low molecular weight protein tyrosine phosphatase (LWM-PTP) isoform B (EC 3.1.3.48). Those candidates that demonstrated comparable or better docking scores than that of pyridoxal 5'-phosphate (PLP), one of the most potent known inhibitors of LMW-PTP with a competitive inhibitor dissociation constant (Kis) of 7.6µM (pH 5.0), were analyzed via in vitro kinetic assays against LMW-PTP isoform B. While none of the compounds tested in vitro was significantly better that PLP, five compounds showed comparable inhibition. These five compounds are very diverse in structure and represent new therapeutic leads for inhibition of this isozyme.

Use of Interactive Simulations in Fundamentals of Biochemistry, a LibreText Online Educational Resource, to Promote Understanding of Dynamic Reactions.

Biology is perhaps the most complex of the sciences, given the incredible variety of chemical species that are interconnected in spatial and temporal pathways that are daunting to understand. Their interconnections lead to emergent properties such as memory, consciousness, and recognition of self and non-self. To understand how these interconnected reactions lead to cellular life characterized by activation, inhibition, regulation, homeostasis, and adaptation, computational analyses and simulations are essential, a fact recognized by the biological communities. At the same time, students struggle to understand and apply binding and kinetic analyses for the simplest reactions such as the irreversible first-order conversion of a single reactant to a product. This likely results from cognitive difficulties in combining structural, chemical, mathematical, and textual descriptions of binding and catalytic reactions. To help students better understand dynamic reactions and their analyses, we have introduced two kinds of interactive graphs and simulations into the online educational resource, Fundamentals of Biochemistry, a multivolume biochemistry textbook that is part of the LibreText collection. One type is available for simple binding and kinetic reactions. The other displays progress curves (concentrations vs time) for both simple reactions and more complex metabolic and signal transduction pathways, including those available through databases using systems biology markup language (SBML) files. Users can move sliders to change dissociation and kinetic constants as well as initial concentrations and see instantaneous changes in the graphs. They can also export data into a spreadsheet for further processing, such as producing derivative Lineweaver-Burk and traditional Michaelis-Menten graphs of initial velocity (v0) vs substrate concentration.

Introducing climate change into the biochemistry and molecular biology curriculum.

Our climate is changing due to anthropogenic emissions of greenhouse gases from the production and use of fossil fuels. Present atmospheric levels of CO2 were last seen 3 million years ago, when planetary temperature sustained high Arctic camels. As scientists and educators, we should feel a professional responsibility to discuss major scientific issues like climate change, and its profound consequences for humanity, with students who look up to us for knowledge and leadership, and who will be most affected in the future. We offer simple to complex backgrounds and examples to enable and encourage biochemistry educators to routinely incorporate this most important topic into their classrooms.

A virtual ELISA to quantitate COVID-19 antibodies in patient serum.

Enzyme-linked immunosorbent assays (ELISAs) are used widely in biotechnology, pharmaceutical, and clinical medicine labs. At the same time, they appear to be underrepresented in chemistry and biochemistry curricula, even though their sensitivity, selectivity, and ease of use would argue for their widespread use. We describe here an online ELISA activity suitable for stand-alone use or in conjunction with an actual wet lab ELISA. Specifically, we offer real and mock data for a hypothetical ELISA to detect plasma antibodies to COVID-19 in infected patients who have had the disease. Much of the activity focuses on chemical and mathematical models to fit ELISA or any macromolecule/ligand binding data, a skill that addresses perhaps the most relevant and difficult learning goal of an ELISA experiment.

A project-based biochemistry laboratory promoting the understanding and uses of fluorescence spectroscopy in the study of biomolecular structures and interactions.

A laboratory project for a first semester biochemistry course is described, which integrates the traditional classroom study of the structure and function of biomolecules with the laboratory study of these molecules using fluorescence spectroscopy. Students are assigned a specific question addressing the stability/function of lipids, proteins, or nucleic acids, and asked to design an experiment to answer the question using fluorescence methodologies. Students study phase equilibria and determine the critical micelle concentration of single chain amphiphiles, the melting point of multilamellar vesicles, and the melting points and thermodynamic constants (K(eq) , ΔG(0) , ΔH(0) and ΔS(0) ) for denaturation of ds-DNA and proteins. In addition, they examine binding properties of proteins. These laboratory experiments are designed to support student learning of the major themes of structure and function in the course.

The pre-health collection within MedEdPORTAL's iCollaborative: helping faculty prepare students for the competencies in the new MCAT(2015) exam.

To help faculty prepare and revise courses in all the disciplines represented in the MCAT(2015) , the American Association of Medical Colleges, through its MedEdPORTAL's iCollaborative, has established the Pre-health Collection, a repository of reviewed web resources that are openly and freely available to faculty, and indirectly through them to students. The Pre-health Collection initiative makes use of the Internet to centralize teaching resources and to help faculty at institutions with fewer available resources to incorporate high quality teaching material specifically reviewed to assist students in obtaining the required pre-health competencies. As biochemistry competencies are increasingly represented in the new exam, it is important to grow the number of quality teaching resources for biochemistry within the portal and to develop a community of users and contributors. A description of the Pre-Health Collection and mechanisms for contributions are presented.

Differentiating biochemistry course laboratories based on student experience.

Content and emphases in undergraduate biochemistry courses can be readily tailored to accommodate the standards of the department in which they are housed, as well as the backgrounds of the students in the courses. A more challenging issue is how to construct laboratory experiences for a class with both chemistry majors, who usually have little or no experience with biochemical techniques and biology and biochemistry majors who do. This manuscript describes a strategy for differentiating biochemistry labs to meet the needs of students with differing backgrounds.