Adaptability of restrained molecular dynamics for tertiary structure prediction: application to Crotalus atrox venom phospholipase A2

In order to assess the adaptability and/or applicability ofthe restrained molecular dynamics (RMD) simulation for buildinga possible tertiary structure of a protein from the X-ray crystalstructure of a family reference protein, the tertiary structureprediction of Crotalus atrox venom phospholipase A₂ (PLA₂) wasattempted based on the X-ray crystal structure of bovine pancreaticPLA₂. For the formation of secondary and tertiary structuresfrom the fully extended starting structure, the RMD simulationwith interatomic distance restraints and torsion angle restraints,which were derived from homologous amino acid sequence regionsin the reference protein, was carried out until the molecularsystem was fully equilibrated. The predicted tertiary structureof C.atrox venom PLA₂ was compared with its X-ray crystal structure,and furthermore the utility of this method was discussed byreference to the similar tertiary structure prediction of ß-trypsinfrom the X-ray crystal structure of an elastase.