Title: Feature functional theory - binding predictor (FFT-BP) for the blind prediction of binding free energies,
Abstract: We present a feature functional theory - binding predictor (FFT-BP) for the
protein-ligand binding affinity prediction. The underpinning assumptions of
FFT-BP are as follows: i) representability: there exists a microscopic feature
vector that can uniquely characterize and distinguish one protein-ligand
complex from another; ii) feature-function relationship: the macroscopic
features, including binding free energy, of a complex is a functional of
microscopic feature vectors; and iii) similarity: molecules with similar
microscopic features have similar macroscopic features, such as binding
affinity. Physical models, such as implicit solvent models and quantum theory,
are utilized to extract microscopic features, while machine learning algorithms
are employed to rank the similarity among protein-ligand complexes. A large
variety of numerical validations and tests confirms the accuracy and robustness
of the proposed FFT-BP model. The root mean square errors (RMSEs) of FFT-BP
blind predictions of a benchmark set of 100 complexes, the PDBBind v2007 core
set of 195 complexes and the PDBBind v2015 core set of 195 complexes are 1.99,
2.02 and 1.92 kcal/mol, respectively. Their corresponding Pearson correlation
coefficients are 0.75, 0.80, and 0.78, respectively.