J. Schlitter et al., TARGETED MOLECULAR-DYNAMICS SIMULATION OF CONFORMATIONAL CHANGE - APPLICATION TO THE T[--]R TRANSITION IN INSULIN, Molecular simulation, 10(2-6), 1993, pp. 291
A novel method to calculate transition pathways between two known prot
ein conformations is presented. It is based on a molecular dynamics si
mulation starting from one conformational state as initial structure a
nd using the other for a directing constraint. The method is exemplifi
ed with the T <-- --> R transition of insulin. The most striking diffe
rence between these conformational states is that in T the 8 N-termina
l residues of the B chain are arranged as an extended strand whereas i
n R they are forming a helix. Both the transition from T to R and from
R to T were simulated. The method proves capable of finding a continu
ous pathway for each direction which are moderately different. The ref
olding processes are illustrated by a series of transient structures a
nd pairs of PHI, PSI angles selected from the time course of the simut
ations. In the T --> R direction the helix is formed in the tast third
of the transition, while in the R --> T direction it is preserved dur
ing more than half of the simutation period. The results are discussed
in comparison with those of an atternative method recently apptied to
the T --> R transition of insulin which is based on targeted energy m
inimisation.