Protein dynamics determined by backbone conformation and atom packing

To study the factors determining the collective motions in thermal, conformational fluctuations of a globular protein, molecular dynamics simulations were performed with a backbone model and an atomic-level model. In the backbone model, only the C alpha atoms were explicitly treated with two types of pairwise interactions assigned between the C alpha atoms; atom-packing interactions to take into account the effect of tight atom packing in the protein interior and chain-restoring interactions to maintain the backbone around the native conformation. A quasi-harmonic method was used to decompose the overall fluctuations into independent, collective modes. The modes assigned to large conformational fluctuations showed a good correlation between the backbone and atomic-level models. From this study, it was suggested that the collective modes were motions in which a protein fluctuates, keeping the tertiary structure around the native one and avoiding backbone overlap and, hence, rough aspects of the collective modes can be derived without details of the atomic interactions. The backbone model is useful in obtaining the overall backbone motions of a protein without heavy simulations, even though the simulation starts from a poorly determined conformation of experiments and in sampling main chain conformations, from which the side chain conformations may be predicted.