Relative stability of protein structures determined by x-ray crystallography or NMR spectroscopy: A molecular dynamics simulation study. Proteins 53

ABSTRACT The relative stability of protein structures determined by either X-ray crystallogra-phy or nuclear magnetic resonance (NMR) spectros-copy has been investigated by using molecular dy-namics simulation techniques. Published structures of 34 proteins containing between 50 and 100 resi-dues have been evaluated. The proteins selected represent a mixture of secondary structure types including all , all , and /. The proteins selected do not contain cysteine–cysteine bridges. In addi-tion, any crystallographic waters, metal ions, cofac-tors, or bound ligands were removed before the systems were simulated. The stability of the struc-tures was evaluated by simulating, under identical conditions, each of the proteins for at least 5 ns in explicit solvent. It is found that not only do NMR-derived structures have, on average, higher inter-nal strain than structures determined by X-ray crys-tallography but that a significant proportion of the structures are unstable and rapidly diverge in simu-lations. Proteins 2003;53:111–120. © 2003Wiley-Liss, Inc. Key words: X-ray crystallography; NMR spectros-copy; molecular dynamic simulation; protein structure; structure refinemen