Pulmonary surfactant protein-D is a water soluble protein belongs to c-type mammalian lectin of collectins super family, have significant role in antimicrobial host-defense mechanism by binding of carbohydrate ligands with its carbohydrate recognition domain. Previous studies explains the contributions of Phe335 to ligand recognition by SP-D and showed site specific substitution of Leu for Phe335 decreased affinities for maltoside and maltotriose without altering affinity for maltose or glucose. However, substitution of Tyr or Trp restored affinity. Taking this into consideration, in our computational model an attempt has been made to study the importance of Phe335 position towards affinity of binding with ligands using Molegro Virtual Docker (MVD). F335G showed high dock score with p-nitrophenyl-alpha-D-maltoside (-96.8654 kcal/mol), pnitrophenyl- beta-D-maltoside (-91.1205kcal/mol) and maltotriose (-81.8233kcal/mol). Further, virtual screening of 62 various mannose derived carbohydrate ligands were carried out and the top three compounds were selected based on the binding affinity with SP-D. It was observed that Arg343 residue interactions predominated in most of the cases. Moreover, Glu321, Asn323, Pro319, Glu329, Asn341 and Asp342 residue interactions were also observed.