Protein Engineering, Vol. 12, No. 12, 1097-1104,
December 1999
© 1999 Oxford University Press
Molecular dynamics model structures for the molten globule state of 
-lactalbumin: aromatic residue clusters I and II
Faculty of Science and Technology, Hirosaki University, 3 Bunkyo-cho, Hirosaki, Aomori 036-8561, Japan
To model the molten globule structure of 
-lactalbumin, molecular dynamics (MD) simulations were carried out for the protein in explicit water at high temperature. In these simulations, long-range Coulomb interactions were evaluated explicitly with an original method (particle–particle and particle–cell: PPPC) to avoid artifacts caused by the cut-off. The MD simulations were started from two initial conditions to verify that similar results would be obtained. From the last 150 ps trajectories of the two MD simulations, two partially unfolded average structures were obtained. These structures had the following common structural features which are characteristic of the molten globule state. The radii of gyration for these conformations were 7.4 and 9.6% larger than that of the native state. These values were almost the same as the experimental value (9.6%) observed recently by small-angle X-ray scattering (Kataoka,M., Kuwajima,K., Tokunaga,F. and Goto,Y., 1997, Protein Sci., 6, 422–430). Furthermore, aromatic residues of clusters I and II in these structures were far apart from each other except for Try103–Trp104. This result is in good agreement with NMR experimental results for the acid-denatured molten globule state (Alexandrescu et al., 1992, 1993); that is, NOE signals between the aromatic residues were not observed, except for that of Try103–Trp104 in the molten globule state. Other structural features of these models for the molten globule state are discussed with reference to native state structures.
Keywords: -lactalbumin/aromatic residue cluster/gyration radius/molecular dynamics/molten globule
1 To whom correspondence should be addressed; email: msaito{at}si.hirosaki-u.ac.jp