Testing the method of crystallographic refinement using molecular dynamics

The method of crystallographic refinement using molecular dynamics [Brünger, Kuriyan & Karplus (1987). Science, 235, 458-460] has been implemented to work with the GROMOS simulation package. It has been tested by applying it to the structure of phospholipase A2. The structure of this molecule had previously been refined at high resolution with conventional methods. The new method successfully refined the initial multi-isomorphous replacement structure, removing most of the errors, without any manual intervention. All the refinement was performed at 300 K. The use of lower-resolution data allows greater conformational transitions to occur whereas the inclusion of high-resolution data results in a more accurate structure.