Protein structural robustness to mutations: an in silico investigation.

Proteins possess qualities of robustness and adaptability to perturbations such as mutations, but occasionally fail to withstand them, resulting in loss of function. Herein, the structural impact of mutations is investigated independently of the functional impact. Primarily, we aim at understanding the mechanisms of structural robustness pre-requisite for functional integrity. The structural changes due to mutations propagate from the site of mutation to residues much more distant than typical scales of chemical interactions, following a cascade mechanism. This can trigger dramatic changes or subtle ones, consistent with a loss of function and disease or the emergence of new functions. Robustness is enhanced by changes producing alternative structures, in good agreement with the view that proteins are dynamic objects fulfilling their functions from a set of conformations. This result, robust alternative structures, is also coherent with epistasis or rescue mutations, or more generally, with non-additive mutational effects and compensatory mutations. To achieve this study, we developed the first algorithm, referred to as Amino Acid Rank (AAR), which follows the structural changes associated with mutations from the site of the mutation to the entire protein structure and quantifies the changes so that mutations can be ranked accordingly. Assessing the paths of changes opens the possibility of assuming secondary mutations for compensatory mechanisms.

The Impact of Online Social Networks on Health and Health Systems: A Scoping Review and Case Studies.

Interaction through online social networks potentially results in the contestation of prevailing ideas about health and health care, and to mass protest where health is put at risk or health care provision is wanting. Through a review of the academic literature and case studies of four social networking health sites (PatientsLikeMe, Mumsnet, Treatment Action Campaign, and My Pro Ana), we establish the extent to which this phenomenon is documented, seek evidence of the prevalence and character of health-related networks, and explore their structure, function, participants, and impact, seeking to understand how they came into being and how they sustain themselves. Results indicate mass protest is not arising from these established health-related networking platforms. There is evidence of changes in policy following campaigning activity prompted by experiences shared through social networking such as improved National Health Service care for miscarriage (a Mumsnet campaign). Platform owners and managers have considerable power to shape these campaigns. Social networking is also influencing health policy indirectly through increasing awareness and so demand for health care. Transient social networking about health on platforms such as Twitter were not included as case studies but may be where the most radical or destabilizing influence on health care policy might arise.