TY - JOUR
T1 - Lin_F9
T2 - A Linear Empirical Scoring Function for Protein-Ligand Docking
AU - Yang, Chao
AU - Zhang, Yingkai
N1 - Funding Information:
This work was supported by the U.S. National Institutes of Health (R35-GM127040). We thank NYU-ITS for providing computational resources.
Publisher Copyright:
© 2021 American Chemical Society.
PY - 2021
Y1 - 2021
N2 - 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/.
AB - 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/.
UR - http://www.scopus.com/inward/record.url?scp=85115096055&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85115096055&partnerID=8YFLogxK
U2 - 10.1021/acs.jcim.1c00737
DO - 10.1021/acs.jcim.1c00737
M3 - Article
AN - SCOPUS:85115096055
JO - Journal of Chemical Information and Modeling
JF - Journal of Chemical Information and Modeling
SN - 1549-9596
ER -