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We study the models submitted to round 12 of the Critical Assessment of protein Structure Prediction (CASP) experiment to assess how well the binding properties are conserved when the X-ray structures of the target proteins are replaced by their models. To explore small molecule binding we generate distributions of molecular probes – which are fragment-sized organic molecules of varying size, shape, and polarity – around the protein, and count the number of interactions between each residue and the probes, resulting in a vector of interactions we call a binding fingerprint. The similarity between two fingerprints, one for the X-ray structure and the other for a model of the protein, is determined by calculating the correlation coefficient between the two vectors. The resulting correlation coefficients are shown to correlate with global measures of accuracy established in CASP, and the relationship yields an accuracy threshold that has to be reached for meaningful binding surface conservation. The clusters formed by the probe molecules reliably predict binding hot spots and ligand binding sites in both X-ray structures and reasonably accurate models of the target, but ensembles of models may be needed for assessing the availability of proper binding pockets. We explored ligand docking to the few targets that had bound ligands in the X-ray structure. More targets were available to assess the ability of the models to reproduce protein–protein interactions by docking both the X-ray structures and models to their interaction partners in complexes. It was shown that this application is more difficult than finding small ligand binding sites, and the success rates heavily depend on the local structure in the potential interface. In particular, predicted conformations of flexible loops are frequently incorrect in otherwise highly accurate models, and may prevent predicting correct protein–protein interactions.

Purpose: We developed an electronic patient-facing family history collection tool including B-RST 3.0, PREMM5 risk assessments and “limited family knowledge/structure” information designed for primary care settings. We evaluated the tool’s performance compared with genetic-counselor-collected information for clinical risk stratification in a population with barriers to access. Methods: English- or Spanish-speaking patients aged 18 to 49 were invited to participate. Individuals with limited family knowledge or at high or moderate risk based on their responses in the tool were offered genetic testing and counseling. We assessed overall agreement of family history collected in the tool compared with family history collected by the genetic counselors using Krippendorff’s alpha (K-alpha). Multivariable logistic regression was used to assess characteristics associated with inaccuracy. Results: Most people (94%, n = 1711) who interacted with the tool completed it. Those included in the agreement analysis (n = 604) had a median age of 36.3 years, 81.6% were female, and 44.4% were Non-Hispanic White. Both the B-RST 3.0 and PREMM5 had moderate agreement: 69.9% (K-alpha = .40, 95% CI [0.32, 0.47]) and 83.9% (K-alpha = .52, 95% CI [0.43, 0.60]), respectively. Agreement was high (96%) for people with clinically significant risk for one of the hereditary cancer syndromes. For B-RST 3.0, the factors significantly associated with inaccuracy were study site, sex, and race/ethnicity. For PREMM5, age, sex, and education were associated with inaccuracy. Barriers to access were not associated with inaccuracy. Conclusion: Implementation of this tool could increase identification of individuals at risk for hereditary cancer syndromes, including those with barriers to health care access.

Objective: To examine the effects of a 6-month weight loss intervention on physical function, inflammatory biomarkers, and metabolic biomarkers in both those with and without osteoarthritis (OA). Design: 59 individuals ≥60 years old with obesity and a functional impairment were enrolled into this IRB approved clinical trial and randomized into one of two 6-month weight loss arms: a higher protein hypocaloric diet or a standard protein hypocaloric diet. All participants were prescribed individualized 500-kcal daily-deficit diets, with a goal of 10% weight loss. Additionally, participants participated in three, low-intensity, exercise sessions per week. Physical function, serum biomarkers and body composition data were assessed at the baseline and 6-month timepoints. Statistical analyses assessed the relationships between biomarkers, physical function, body composition, and OA status as a result of the intervention. Results: No group effects of dietary intervention were detected on any outcome measures (multiple p ​> ​0.05). During the 6-month trial, participants lost 6.2 ​± ​4.0% of their bodyweight (p ​

Background: We conducted a survey in an online forum without prior IRB approval which yielded information we wanted to share with the medical community. We sought approaches to ethically publish the survey's results. Objective: Address the ethical issues raised by considering publication of community forum perspectives without prior regulatory oversight or written informed consent. Methods: A research ethics consultation identified two approaches: 1) assessing community perspectives in general on academic publication and 2) obtaining a collaborative ethics consultation to promote diversity in identifying ethical considerations. Results: Most community respondents were in favor of the concept of publication, noting the value of patient perspectives to improve communication, clinical relationships, and care. Considerations identified by the Collaborative included whether publication is likely to have value, would cause harm to participants, and whether publication would threaten trust. The role of formal oversight was reviewed. Conclusions: There is a reasonable ethical justification for publishing insights gained from a community forum based on evidence of community support for, and value to the community of, the publication, even when prior regulatory oversight was not obtained. Proactive strategies can be applied to obviate this issue.