REFINED SOLUTION STRUCTURE OF AL3-THYMULIN COMPLEXES BASED ON RESTRAINED MOLECULAR-DYNAMICS CALCULATIONS()

We report the solution three-dimensional structure of complexes of Al3 + with thymulin, a linear nonapeptide of thymic origin isolated from s erum. Structural determination was performed by distance geometry and molecular dynamics calculations in a DMSO solvent box, by using NOE-de rived distance restraints. Two distinct conformers (parallel and antip arallel), as a consequence of aluminum coordination, were characterize d. A tightly folded structure appears for both conformers with several gamma-turns and a loop region stabilized by aluminum coordination via the Ser(4)OH and the Asn(9)COO(-) groups and by several intra-and int ermolecular interactions. Comparison of the solution structures of the se two complexes suggests that the antiparallel isomer should be mainl y present in solution.