Abstract: NMT is a promising target for the development of novel anfifungal agents with a new mode of action. In order to know the important functional residues and regions in the active site of Candida albicans N-myristoyltransferase(CaNMT) in detail, multiple copy simultaneous search(MCSS) was used to identify the hydrophobic pockets, hydrogen-bonding sites and electrostatic negative sites. The results from MCSS calculation reveal that there were two hydrophobic pockets. One pocket was lined with Tyr107, Tyr119, Val108, Phe117, Phe123, Ala127, Phe176 and Leu33, the other pocket was lined with Phe115, Phe240 and Phe339. Moreover, two hydrogen-bonding sites were identified by MCSS calculations. Among those hydrogen-bonding residues, Tyr119, His227, Asn392 and Leu451 could form hydrogen bond with the benzofuran inhibitors and Tyr107, Asn175, Thr211 and Asp412 were newly discovered hydrogen-bonding residues, which were highly conserved residues across the NMT family and would play an important role in the design of NMT inhibitors with novel chemical scaffold. Important functional residue Leu451 could serve as both hydrogen-bonding site and electrostatic negative site, which was indispensable in inhibitor design. The above results could provide important clues for the de novo design and virtual high-throughput screening of novel NMT inhibitors.

Key words: N-Myristoyltransferase, Antifungal, Multiple copy simultaneous search, Drug binding site, Drug design