@article{TEXTUAL,
      recid = {7496},
      author = {Shen, Rong and Han, Wei and Fiorin, Giacomo and Islam,  Shahidul M. and Schulten, Klaus and Roux, Benoît},
      title = {Structural Refinement of Proteins by Restrained Molecular  Dynamics Simulations with Non-interacting Molecular  Fragments},
      journal = {PLOS ONE},
      address = {2015-10-27},
      number = {TEXTUAL},
      abstract = {The knowledge of multiple conformational states is a  prerequisite to understand the function of membrane  transport proteins. Unfortunately, the determination of  detailed atomic structures for all these functionally  important conformational states with conventional  high-resolution approaches is often difficult and  unsuccessful. In some cases, biophysical and biochemical  approaches can provide important complementary structural  information that can be exploited with the help of advanced  computational methods to derive structural models of  specific conformational states. In particular, functional  and spectroscopic measurements in combination with  site-directed mutations constitute one important source of  information to obtain these mixed-resolution structural  models. A very common problem with this strategy, however,  is the difficulty to simultaneously integrate all the  information from multiple independent experiments involving  different mutations or chemical labels to derive a unique  structural model consistent with the data. To resolve this  issue, a novel restrained molecular dynamics structural  refinement method is developed to simultaneously  incorporate multiple experimentally determined constraints  (e.g., engineered metal bridges or spin-labels), each  treated as an individual molecular fragment with all atomic  details. The internal structure of each of the molecular  fragments is treated realistically, while there is no  interaction between different molecular fragments to avoid  unphysical steric clashes. The information from all the  molecular fragments is exploited simultaneously to  constrain the backbone to refine a three-dimensional model  of the conformational state of the protein. The method is  illustrated by refining the structure of the  voltage-sensing domain (VSD) of the Kv1.2 potassium channel  in the resting state and by exploring the distance  histograms between spin-labels attached to T4 lysozyme. The  resulting VSD structures are in good agreement with the  consensus model of the resting state VSD and the spin-spin  distance histograms from ESR/DEER experiments on T4  lysozyme are accurately reproduced.},
      url = {http://knowledge.uchicago.edu/record/7496},
}