Domain movements in human fatty acid synthase by quantized elastic deformational model.

This paper reports the results of applying a computational method called the quantized elastic deformational model, to the determination of conformational flexibility of the supermolecular complex of human fatty acid synthase. The essence of this method is the ability to model large-scale conformational changes such as domain movements by treating the protein as an elastic object without the knowledge of protein primary sequence and atomic coordinates. The calculation was based on the electron density maps of the synthase at 19 A. The results suggest that the synthase is a very flexible molecule. Two types of flexible hinges in the structure were identified. One is an intersubunit hinge formed by the intersubunit connection and the other is an intrasubunit hinge located between domains I and II. Despite the fact that the dimeric synthase has a chemically symmetric structure, large domain movements around the hinge region occur in various directions and allow the molecule to adopt a wide range of conformations. These domain movements are likely to be important in facilitating and regulating the entire palmitate synthesis by coordinating the communication between components of the molecule, for instance, adjusting the distance between various active sites inside the catalytic reaction center. Finally, the ability to describe protein motions of a supermolecular complex, without the information of protein sequence and atomic coordinates, is a major advance in computational modeling of protein dynamics. The method provides an unprecedented ability to model protein motions at such a low resolution of structure.