The CAPRI and CASP prediction experiments have demonstrated the power of community wide tests of methodology in assessing the current state of the art and spurring progress in the very challenging areas of protein docking and structure prediction. We sought to bring the power of community wide experiments to bear on a very challenging protein design problem that provides a complementary but equally fundamental test of current understanding of protein-binding thermodynamics. We have generated a number of designed protein-protein interfaces with very favorable computed binding energies but which do not appear to be formed in experiments, suggesting there may be important physical chemistry missing in the energy calculations. 28 research groups took up the challenge of determining what is missing: we provided structures of 87 designed complexes and 120 naturally occurring complexes and asked participants to identify energetic contributions and/or structural features that distinguish between the two sets. The community found that electrostatics and solvation terms partially distinguish the designs from the natural complexes, largely due to the non-polar character of the designed interactions. Beyond this polarity difference, the community found that the designed binding surfaces were on average structurally less embedded in the designed monomers, suggesting that backbone conformational rigidity at the designed surface is important for realization of the designed function. These results can be used to improve computational design strategies, but there is still much to be learned; for example, one designed complex, which does form in experiments, was classified by all metrics as a non-binder.
Suicidal ideation detection in online social networks is an emerging research area with major challenges. Recent research has shown that the publicly available information spread across social media platforms holds valuable indicators to effectively detecting individuals with suicidal intentions. The key challenge of suicide prevention is understanding and detecting the complex risk factors and warning signs that may precipitate the event. In this paper, we present a new approach that uses the social media platform Twitter to quantify suicide-warning signs for individuals and to detect posts containing suicide-related content. The main originality of this approach is the automatic identification of sudden changes in a user's online behavior. To detect such changes, we combine natural language processing techniques to aggregate behavioral and textual features and pass these features through a martingale framework, which is widely used for change detection in data streams. Experiments show that our text-scoring approach effectively captures warning signs in text compared to traditional machine learning classifiers. Additionally, the application of the martingale framework highlights changes in online behavior and shows promise for detecting behavioral changes in at-risk individuals.
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