Structure-Based Predictive Models for Allosteric Hot Spots
Figure 4
Hotspot predictions mapped to the inactive state structure of lac repressor.
(A) Predictions made by the top 9 highest-precision Hybrid Feature Set models according to the voting scheme for lac repressor mapped onto the inactive state structure (1tlf). Experimentally tested residues rendered in van der Waals spheres, with known non-hotspots in small van der Waals spheres and known hotspots in larger ones. For other residues, the prediction is shown along the backbone trace, but no experimental data is available to test the prediction. Each residue in the structure is colored according to a blue→green→red heat map, where the extremes are as follows: red represents residues predicted to be hotspots by 9/9 of the models and blue residues to be predicted hotspots by 0/9 models (predicted non-hotspots by 9/9 models). (Refer to color bar above for exact mapping of the number of predicted hotspots to the color.) For ease of viewing only one set of dimers (chain A and B) is shown. His 74 and Asp 278, residues not in the independent data set but were studied experimentally and found to be allosterically active, are rendered in van der Waals mode as well [63]. Correct positive (hotspot) and negative (non-hotspot) predictions are colored according to the heat map, while false predictions are colored gray. The inducer molecule IPTG is rendered as sticks and colored by element. (B) Here the complete set of residues that caused the IS phenotype are rendered in van der Waals spheres. The hotspots depicted in A. are a subset of these for which no substitution caused an I− phenotype (completely nonfunctional). Incorrect predictions, i.e. false negatives, are colored in gray.