Community-Wide Assessment of Protein-Interface Modeling Suggests Improvements to Design Methodology

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

Ato eno kyokan o kashika kachika kano ka?

Structural colors are a result of the scattering of certain frequencies of the incident light on micro- or nanoscale features in a material. This is a quite different phenomenon from that of colors produced by absorption of different frequencies of the visible spectrum by pigments or dyes, which is the most common way of coloring used in our daily life. However, structural colors are more robust and can be engineered to span most of the visible spectrum without changing the base material, only its internal structure. They are abundant in nature, with examples as colorful as beetle shells and butterfly wings, but there are few ways of preparing them for large-scale commercial applications for real-world uses. In this work, we present a technique to create a full gamut of structural colors based on a low-cost, robust, and scalable fabrication of periodic network structures in porous alumina as well as the strategy to theoretically predict and engineer different colors on demand. We experimentally demonstrate mesoporous network metamaterial structures with engineered colors spanning the whole optical spectrum and discuss their applications in sensing, environmental monitoring, biomimetic tissues engineering, etc

Blind prediction of interfacial water positions in CAPRI

We report the first assessment of blind predictions of water positions at protein-protein interfaces, performed as part of the critical assessment of predicted interactions (CAPRI) community-wide experiment. Groups submitting docking predictions for the complex of the DNase domain of colicin E2 and Im2 immunity protein (CAPRI Target 47), were invited to predict the positions of interfacial water molecules using the method of their choice. The predictions-20 groups submitted a total of 195 models-were assessed by measuring the recall fraction of water-mediated protein contacts. Of the 176 high- or medium-quality docking models-a very good docking performance per se-only 44% had a recall fraction above 0.3, and a mere 6% above 0.5. The actual water positions were in general predicted to an accuracy level no better than 1.5 angstrom, and even in good models about half of the contacts represented false positives. This notwithstanding, three hotspot interface water positions were quite well predicted, and so was one of the water positions that is believed to stabilize the loop that confers specificity in these complexes. Overall the best interface water predictions was achieved by groups that also produced high-quality docking models, indicating that accurate modelling of the protein portion is a determinant factor. The use of established molecular mechanics force fields, coupled to sampling and optimization procedures also seemed to confer an advantage. Insights gained from this analysis should help improve the prediction of protein-water interactions and their role in stabilizing protein complexes. Proteins 2014; 82:620-632. (c) 2013 Wiley Periodicals, Inc