Can molecular dynamics simulations provide high-resolution refinement of protein structure?
Chen J; Brooks CL Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA. Recent advances in efficient and accurate treatment of solvent with the generalized Born approximation (GB) have made it possible to substantially refine the protein structures generated by various prediction tools through detailed molecular dynamics simulations. As demonstrated in a recent CASPR experiment, improvement can be quite reliably achieved when the initial models are sufficiently close to the native basin (e.g., 3-4 A C(alpha) RMSD). A key element to effective refinement is to incorporate reliable structural information into the simulation protocol. Without intimate knowledge of the target and prediction protocol used to generate the initial structural models, it can be assumed that the regular secondary structure elements (helices and strands) and overall fold topology are largely correct to start with, such that the protocol limits itself to the scope of refi
