Lin_F9: A Linear Empirical Scoring Function for Protein–Ligand Docking
Chao Yang, Yingkai Zhang · Journal of Chemical Information and Modeling · 2021
Molecular docking is one of the most widely used computational tools in structure-based drug design and is critically dependent on accuracy and robustness of the scoring function. In this work, we introduce a new scoring function Lin_F9, which is a linear combination of nine empirical terms, including a unified metal bond term to specifically describe metal–ligand interactions. Parameters in Lin_F9 are obtained with a multistage fitting protocol using explicit water-included structures. For the CASF-2016 benchmark test set, Lin_F9 achieves the top scoring power among all 34 classical scoring functions for both original crystal poses and locally optimized poses with Pearson correlation coefficients ( R ) of 0.680 and 0.687, respectively. Meanwhile, in comparison with Vina, Lin_F9 achieves consistently better scoring power and ranking power with various types of protein–ligand complex structures that mimic real docking applications, including end-to-end flexible docking for the CASF-2016 benchmark test set using a single or an ensemble of protein receptor structures, as well as for D3R Grand Challenge (GC4) test sets. Lin_F9 has been implemented in a fork of Smina as an optional built-in scoring function that can be used for docking applications as well as for further improvement of scoring functions and docking protocols. Lin_F9 is accessible through https://yzhang.hpc.nyu.edu/Lin_F9/ .