Prediction of protein assemblies, the next frontier: The CASP14-CAPRI experiment.

We present the results for CAPRI Round 50, the fourth joint CASP-CAPRI protein assembly prediction challenge. The Round comprised a total of twelve targets, including six dimers, three trimers, and three higher-order oligomers. Four of these were easy targets, for which good structural templates were available either for the full assembly, or for the main interfaces (of the higher-order oligomers). Eight were difficult targets for which only distantly related templates were found for the individual subunits. Twenty-five CAPRI groups including eight automatic servers submitted ~1250 models per target. Twenty groups including six servers participated in the CAPRI scoring challenge submitted ~190 models per target. The accuracy of the predicted models was evaluated using the classical CAPRI criteria. The prediction performance was measured by a weighted scoring scheme that takes into account the number of models of acceptable quality or higher submitted by each group as part of their five top-ranking models. Compared to the previous CASP-CAPRI challenge, top performing groups submitted such models for a larger fraction (70-75%) of the targets in this Round, but fewer of these models were of high accuracy. Scorer groups achieved stronger performance with more groups submitting correct models for 70-80% of the targets or achieving high accuracy predictions. Servers performed less well in general, except for the MDOCKPP and LZERD servers, who performed on par with human groups. In addition to these results, major advances in methodology are discussed, providing an informative overview of where the prediction of protein assemblies currently stands.

Hydrophobic hydration and pairwise hydrophobic interaction of Lennard-Jones and Mie particles in different water models.

The study provides a deep computational analysis of the thermodynamic and structural features associated with the hydration of xenon, Xe, and its pairwise hydrophobic interaction (i.e., the potential of mean force, PMF), over a large temperature range. Xe is described both as a Lennard-Jones particle, LJ-Xe, and as a Mie particle, Mie-Xe (pseudo hard sphere). Three different water models are used: TIP3P-Ew, SPCE and TIP4P-2005. Mie-Xe is more hydrophobic than LJ-Xe due to the lack of the attractive energetic interactions with water molecules; its hydration, around room temperature, is opposed by a large and negative entropy change and a positive enthalpy change. The PMF of Mie-Xe is characterized by a deep minimum at contact distance whose depth increases with temperature, and whose magnitude is significantly larger than that obtained for LJ-Xe. The contact minimum configuration of Mie-Xe is favoured by a large positive entropy change and contrasted by a positive enthalpy change. These results are qualitatively the same regardless of the water model used. There is no clear connection between the values determined for the thermodynamic functions and the structural features of the hydration shells surrounding the single Mie-Xe and the couple of Mie-Xe particles in the contact minimum configuration. This confirms that the structural reorganization of water associated with such processes is characterized by an almost complete enthalpy-entropy compensation.