title: The VSGB 2.0 model: a next generation energy model for high resolution protein structure modeling.
abstract: A novel energy model (VSGB 2.0) for high resolution protein structure modeling is described, which features an optimized implicit solvent model as well as physics-based corrections for hydrogen bonding, π-π interactions, self-contact interactions, and hydrophobic interactions. Parameters of the VSGB 2.0 model were fit to a crystallographic database of 2239 single side chain and 100 11-13 residue loop predictions. Combined with an advanced method of sampling and a robust algorithm for protonation state assignment, the VSGB 2.0 model was validated by predicting 115 super long loops up to 20 residues. Despite the dramatically increasing difficulty in reconstructing longer loops, a high accuracy was achieved: all of the lowest energy conformations have global backbone RMSDs better than 2.0 Å from the native conformations. Average global backbone RMSDs of the predictions are 0.51, 0.63, 0.70, 0.62, 0.80, 1.41, and 1.59 Å for 14, 15, 16, 17, 18, 19, and 20 residue loop predictions, respectively. When these results are corrected for possible statistical bias as explained in the text, the average global backbone RMSDs are 0.61, 0.71, 0.86, 0.62, 1.06, 1.67, and 1.59 Å. Given the precision and robustness of the calculations, we believe that the VSGB 2.0 model is suitable to tackle "real" problems, such as biological function modeling and structure-based drug discovery.
authors: Department of Chemistry, Columbia University, New York, New York 10027, USA.
authors: Jianing
authors: J
authors: Li
authors: Robert
authors: R
authors: Abel
authors: Kai
authors: K
authors: Zhu
authors: Yixiang
authors: Y
authors: Cao
authors: Suwen
authors: S
authors: Zhao
authors: Richard A
authors: RA
authors: Friesner
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins