Computer simulations of the dynamics of human choriogonadotropin and its alpha subunit

Human choriogonadotropin (hCG) belongs to a family of heterodimeric glycopr otein hormones involved in reproduction. Over 75 ns of molecular dynamics s imulations of this heterodimer and the free alpha subunit were performed an d validated by experimental information to arrive at a qualitative dynamica l description of these molecules. A number of 5-ns simulations at 400 degre es K describe a sufficiently stable heterodimer structure, whereas the free a subunit shows the experimentally observed partial unfolding. From the ma in collective fluctuations of the free alpha subunit, it can be derived tha t residues alpha 35-55 form a domain that is highly flexible with respect t o the other domain, which contains all five disulfide bonds, The apparent l oss of secondary structure in the region alpha 33-58 may very well be induc ed by this. Dynamic domains can also be determined from the hCG heterodimer simulations. The most important collective mode of motion shows that the f lexibility of the alpha subunit is reduced by concerted rotation with both the long loop and the determinant loop of the beta subunit, The motion of t he free or subunit does not differ significantly from the motion it has in the hCG heterodimer, but the amplitudes along the most important eigenvecto rs are larger. Proteins 1999;37:668-682. (C) 1999 Wiley-Liss, Inc.