Our journey to the cave – adventures by balloon

Publisher PD

Accurate prediction of dynamic protein-ligand binding using P-score ranking

Protein–ligand binding prediction typically relies on docking methodologies and associated scoring functions to propose the binding mode of a ligand in a biological target. Significant challenges are associated with this approach, including the flexibility of the protein–ligand system, solvent-mediated interactions, and associated entropy changes. In addition, scoring functions are only weakly accurate due to the short time required for calculating enthalpic and entropic binding interactions. The workflow described here attempts to address these limitations by combining supervised molecular dynamics with dynamical averaging quantum mechanics fragment molecular orbital. This combination significantly increased the ability to predict the experimental binding structure of protein–ligand complexes independent from the starting position of the ligands or the binding site conformation. We found that the predictive power could be enhanced by combining the residence time and interaction energies as descriptors in a novel scoring function named the P-score. This is illustrated using six different protein–ligand targets as case studies.</p

Accurate prediction of dynamic protein-ligand binding using P-score ranking

Protein–ligand binding prediction typically relies on docking methodologies and associated scoring functions to propose the binding mode of a ligand in a biological target. Significant challenges are associated with this approach, including the flexibility of the protein–ligand system, solvent-mediated interactions, and associated entropy changes. In addition, scoring functions are only weakly accurate due to the short time required for calculating enthalpic and entropic binding interactions. The workflow described here attempts to address these limitations by combining supervised molecular dynamics with dynamical averaging quantum mechanics fragment molecular orbital. This combination significantly increased the ability to predict the experimental binding structure of protein–ligand complexes independent from the starting position of the ligands or the binding site conformation. We found that the predictive power could be enhanced by combining the residence time and interaction energies as descriptors in a novel scoring function named the P-score. This is illustrated using six different protein–ligand targets as case studies.</p

Theory and research on bullying and racism from an Aboriginal Australian perspective

This paper offers a brief review of research on the impact of bullying and racism on Aboriginal and Torres Strait Islander peoples within Australia. The overarching emphasis was on the variety of physical, social, mental, and educational outcomes for Aboriginal and Torres Strait Islander children and youth, whilst also critiquing the prevailing literature with regard to its inclusion and sensitivity towards the importance of culture and connected values. Within the Aboriginal and Torres Strait Islander research setting, although a strong base of research on the impact of racism has emerged, research on the impact of bullying is more recent. In addition, while there may be considerable overlap as to the individual impact of bullying and racism, racism research has identified a wider cultural/identity-threat that bullying research (with a few exceptions) has largely ignored. As a result, there is a need to be sensitive to cultural differences with regard to both the types and effects of racism and bullying, and that efforts to understand and to lessen the prevalence of racism and bullying should be framed within the development of a culturally sensitive and secure framework (Coffin, 2008)

Dundee Annual Neurosurgery Skills Event (DANSE) — improving the availability and affordability of neurosurgical skills workshops for medical students

Background: Neurosurgery can be a daunting career choice for medical students, with preparation for trainee application often being inaccessible and expensive. This article describes a student-led neurosurgical skills event supported by local neurosurgery faculty members. Such event was designed to offer a means to bridge this gap by providing an opportunity to practice neurosurgical techniques in simulation, and learn about what a career in neurosurgery involves. Methods: Pre- and postskills laboratory surveys were used to ascertain the baseline confidence and knowledge of common neurosurgical techniques, as well as to what both the application to neurosurgery and the typical workload of a neurosurgeon involves. The conference offered six neurosurgical workshops as well as three lectures to provide practical and theoretical learning opportunities. The session included introduction to the candidates and faculty, identification of learning objectives, and career discussion. Postcourse feedback also was also used to assess learning outcomes. Results: Eighteen students attended the event. Postskills event, students were significantly more likely to understand the principles behind all of the relevant neurosurgical skills included on the day. Additionally, students were more likely to understand what a career in neurosurgery involves, and how to approach applying for a training number. Respondents enjoyed the workshops, valued hands-on experience and interactions with consultants, found it affordable, and would recommend to their peers. Conclusions: For medical students interested in a career in neurosurgery, opportunities to learn relevant techniques and skills are often expensive and difficult to come across. Here, we highlight affordable methods of simulation to result in significant student satisfaction. Additionally, providing ample opportunity to practice different neurosurgical techniques under almost 1:1 level tutoring enables significant increases in students' confidence and understanding of different neurosurgical concepts. We greatly encourage other medical student groups to develop their own hands-on simulation events to attract medical students to a surgical field often considered daunting and inaccessible, and address gaps in the medical school curriculum

A bad hangover won’t just hurt your head – it’s damaging the country as well.

If you're feeling the ill effects after a few too many pints at the weekend, your drinking is probably doing more than hurting your head: it’s doing damage to the economy as well. A new study from the US Centres for Disease Control and Prevention has calculated the cost of binge drinking to the national finances, putting the total burden of excessive booze on the US economy at $249 billion (€219 billion at today’s rates) in 2010.......