Wei Zhang - Grow to Fit Molecular Dynamics (G2FMD): an ab initio method for protein side-chain assignment and refinement.

Version 1

      Publication Details (including relevant citation   information):

      Protein Eng   Des Sel. 2006 Feb;19(2):55-65. Epub 2006 Jan 9.


           The rough energy landscapes and tight   packing of protein interiors are two of the critical factors that   have prevented the wide application of physics-based models in   protein side-chain assignment and protein structure prediction in   general. Complementing the rotamer-based methods, we propose an   ab initio method that utilizes molecular mechanics simulations   for protein side-chain assignment and refinement. By reducing the   side-chain size, a smooth energy landscape was obtained owing to   the increased distances between the side chains. The side chains   then gradually grow back during molecular dynamics simulations   while adjusting to their surrounding driven by the interaction   energies. The method overcomes the barriers due to tight packing   that limit conformational sampling of physics-based models. A key   feature of this approach is that the resulting structures are   free from steric collisions and allow the application of all-atom   models in the subsequent refinement. Tests on a small set of   proteins showed nearly 100% accuracy on both chi1 and chi2 of   buried residues and 94% of them were within 20 degrees from the   native conformation, 79% were within 10 degrees and 42% were   within 5 degrees . However, the accuracy decreased when exposed   side chains were involved. Further improvement and application of   the method and the possible reasons that affect the accuracy on   the exposed side chains are discussed.

      Address (URL): http://www.ncbi.nlm.nih.gov/pubmed/16401632