Virtual Molecule: P0 Myelin Glycoprotein. I. Homology Modeling and Prediction of the Secondary and Tertiary Structure - Molecules: Nucleation, Aggregation and Crystallization - page 252

Fig. 11. A calculation of the total energy (the total energy of any molecule is a sum of
chemical energy of bonds, torsion energy, electrostatic energy, and so on) of the P0_Ex
subunit after breaking of the S-S bridge and during the “opening” process. The P0_Ex_a,
P0_Ex_b, P0_Ex_c and P0_Ex_d models correspond with the A, B, C and D models in
Fig. 10. More stable structures have lower total energy. The closed protein (model A) is
the most stable structure. Wide opening causes more unfavorable interactions with the
aquatic environment (particularly interactions between non-bonded atoms and atomic
bonds). In this calculation all hydrogen atoms are neglected.
The 25 Ser … 33 Ile loop is situated on the top of the P0_Ex subunit, close
to the surface of the next myelin layer (Figs. 7A and 9) (Shapiro et al ., 1996).
Breaking the 21 Cys-S—S- 98 Cys disulfide bridge can cause the “opening”
of the P0_Ex part of the protein, where the 1 Ile … 24 Trp part is movable, the
34 Ser … 19 Glu part is anchored in the membrane, and the 25 Ser … 33 Ile loop
functions like a hinge, connecting these two parts of the protein and allows
the wide angle of rotation between them (Figs. 9 and 11). Strongly
hydrophobic residues constitute the central part of the P0_Ex subunit
(the hydrophobic core of the molecule). Spontaneous opening in a natural
hydrophilic environment is difficult (Fig. 11). But strongly hydrophobic
interactions in an opening pocket (Fig. 10(II B), 10(II C), 10(II D) and
10(III B), 10(III C), 10(III D)) can be neutralized by molecules of detergent
or phospholipids. Packing of phospholipids into the hydrophobic pocket
and interactions with detergent can effectively stabilize the structure of
the “opened” P0_Ex subunit (Sedzik et al ., 1999).
Three models of “opening” P0 protein have been built in the follow-
ing research to ascertain possible phases of opening (Fig. 10) and calcu-
late the theoretical energy of the models at each step of the opening of the
dehiscent protein (Fig. 11).
It is well known that the molecule is stable when the interaction
energy between atoms comprising the molecule is at the global minimum