The KH3 domain of Nova-2 protein can precisely recognize the sequence-specific target RNA of human glycine receptor alpha 2. However, the recognition mechanism between the protein and its target RNA is still hotly debated. In this study, molecular dynamic simulations in explicit solvent were utilized to understand the recognition mechanism. The structural analysis and the KolmogorovSmirnov P-test statistics reveal that the KH3 domain might obey a conformational selection mechanism upon RNA binding. However, the induced fit mechanism could not be completely ruled out. Unfolding kinetics indicates that the folding of RNA and KH3 happens first and then the binding between RNA and KH3 follows. Principle component analysis shows that the invariant Gly-Lys-Gly-Gly loop moves toward to the RNA molecule but the C-terminal domain moves away from the RNA molecule upon binding. These specific dominant motions were hypothesized to stabilize the complex structure. The hydrophobic and hydrogen bonding interactions were found to be the driving forces for the specific recognition, in contrast to the dominant electrostatic interactions for nonspecific recognition.