J Chem Inf Model. 2021 Sep 01.
Nucleic acid-ligand interactions play an important role in numerous cellular processes such as gene function expression and regulation. Therefore, nucleic acids such as RNAs have become more and more important drug targets, where the structural determination of nucleic acid-ligand complexes is pivotal for understanding their functions and thus developing therapeutic interventions. Molecular docking has been a useful computational tool in predicting the complex structure between molecules. However, although a number of docking algorithms have been developed for protein-ligand interactions, only a few docking programs were presented for nucleic acid-ligand interactions. Here, we have developed a fast nucleic acid-ligand docking algorithm, named NLDock, by implementing our intrinsic scoring function ITScoreNL for nucleic acid-ligand interactions into a modified version of the MDock program. NLDock was extensively evaluated on four test sets and compared with five other state-of-the-art docking algorithms including AutoDock, DOCK 6, rDock, GOLD, and Glide. It was shown that our NLDock algorithm obtained a significantly better performance than the other docking programs in binding mode predictions and achieved the success rates of 73%, 36%, and 32% on the largest test set of 77 complexes for local rigid-, local flexible-, and global flexible-ligand docking, respectively. In addition, our NLDock approach is also computationally efficient and consumed an average of as short as 0.97 and 2.08 min for a local flexible-ligand docking job and a global flexible-ligand docking job, respectively. These results suggest the good performance of our NLDock in both docking accuracy and computational efficiency.