MOLECULAR-DYNAMICS SIMULATIONS OF THE UNFOLDING OF APOMYOGLOBIN IN WATER

Molecular dynamics simulations of apomyoglobin have been conducted in aqueous solution for 350 ps at 25-degrees-C and for 500 ps in two diff erent runs at 85-degrees-C. The structures obtained at the higher temp erature display properties similar to those of molten globules. Close agreement is obtained between the computed structural models and exper imental data on the helical content of both native apomyoglobin and th e low-pH unfolding intermediate. The results also suggest explanations for the surprising observations on the effects of mutations at the in terface of the A, G, and H helices. Detailed analyses of the final str uctures and the unfolding pathways at high temperature clearly show th at the most stable alpha-helical regions are those in contact with oth er helices.