What are the different refinement levels really doing?
There are two different optimization approaches available within MODELLER: variable target function method (VTFM) with conjugate gradients (CG) [Šali & Blundell, 1993] and molecular dynamics (MD) with simulated annealing (SA) [Šali & Blundell, 1993]. They can both be done to a different degree (with more or less cycles of CG and MD, faster or slower schedule for VTFM and SA). The exact details are best obtained from the scripts themselves because a detailed description would probably be longer than the scripts. For example, the QUANTA and INSIGHTII implementations of MODELLER have these three levels of optimization: no optimization (only copying coordinates from templates and building the undefined atoms using internal geometry information from the RTF entries); only VTFM with CG; also MD with SA. Most of the time (70%) is spent on the MD&SA part. Our experience is that when MD&SA are used, if there are violations in the best of the 10 models, they probably come from an alignment error
