A correlation-based method for the enhancement of scoring functions on funnel-shaped energy landscapes

A correlation-based approach is introduced for enhancing the ability of structure-scoring methods to identify and distinguish native-like conformations. The proposed method relies on a funnel-shaped scoring function that decreases steadily toward the native state. It takes advantage of the idea that the structure from a given ensemble that is closest to the native basin leads to the highest correlation coefficient between a given score and distance to that structure as an approximation of the native state for the entire ensemble. The method is applied successfully to a number of different test cases that demonstrate substantial improvements in the correlation of the score with the distance from the true native state but also result in the selection of more native-like structures compared to the original score.