Human parainfluenza virus type 3 (hPIV-3) is a clinically-significant pathogen and is the causative agent of pneumonia and bronchiolitis in children. In this study the solution dynamics of human parainfluenza type 3 haemagglutinin-neuraminidase (HN) have been investigated. A flexible loop around Asp216 that adopts an open conformation in direct vicinity of the active site of the apo-form of the protein and closes upon inhibitor binding has been identified. To date, no available X-ray crystal structure has shown the molecular dynamic simulation-derived predominant loop-conformation states found in the present study. The outcomes of this study provide additional insight into the dynamical properties of hPIV-3 HN and may have important implications in defining HN glycan recognition events, receptor specificity and anti-parainfluenza virus drug discovery.