NLDock: a Fast Nucleic Acid–Ligand Docking Algorithm for Modeling RNA/DNA–Ligand Complexes

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.