Non-histone chromosomal proteins are an important part of nuclear structure and function due to their ability to interact with DNA to form and modulate chromatin structure and regulate gene expression. However, the understanding of the function of chromosomal proteins at the molecular level has been hampered by the lack of structures of chromosomal protein-DNA complexes. We have carried out a molecular dynamics modeling study to provide insight into the mode of DNA binding to the chromosomal HMG-domain protein, HMG-D. Three models of a complex of HMG-D bound to DNA were derived through docking the protein to two different DNA fragments of known structure. Molecular dynamics simulations of the complexes provided data indicating the most favorable model. This model was further refined by molecular dynamics simulation and extensively analyzed. The structure of the corresponding HMG-D-DNA complex exhibits many features seen in the NMR structures of the sequence-specific HMGdomain-DNA complexes, lymphoid enhancer factor 1 (LEF-1) and testis determining factor (SRY). The model reveals differences from these known structures that suggest how chromosomal proteins bind to many different DNA sequences with comparable affinity. Proteins 30:113-135, 1998.