RosettaHoles2: A volumetric packing measure for protein structure refinement and validation

We present an improved version of RosettaHoles, a methodology for quantitative and visual characterization of protein core packing. RosettaHoles2 features a packing measure more rapidly computable, accurate and physically transparent, as well as a new validation score intended for structures submitted to the Protein Data Bank. The differential packing measure is parameterized to maximize the gap between computationally generated and experimentally determined X‐ray structures, and can be used in refinement of protein structure models. The parameters of the model provide insight into components missing in current force fields, and the validation score gives an upper bound on the X‐ray resolution of Protein Data Bank structures; a crystal structure should have a validation score as good as or better than its resolution.

[1]  F. A. Cotton,et al.  Staphylococcal nuclease: proposed mechanism of action based on structure of enzyme-thymidine 3',5'-bisphosphate-calcium ion complex at 1.5-A resolution. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[2]  C. Sander,et al.  Errors in protein structures , 1996, Nature.

[3]  M. Karplus,et al.  Effective energy function for proteins in solution , 1999, Proteins.

[4]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[5]  V. Calderone,et al.  High-resolution structures of retinol-binding protein in complex with retinol: pH-induced protein structural changes in the crystal state. , 2003, Journal of molecular biology.

[6]  M. Simon,et al.  Helical shifts generate two distinct conformers in the atomic resolution structure of the CheA phosphotransferase domain from Thermotoga maritima. , 2004, Journal of molecular biology.

[7]  Herbert Edelsbrunner,et al.  The geometry of biomolecular solvation , 2005 .

[8]  Jack Snoeyink,et al.  Nucleic Acids Research Advance Access published April 22, 2007 MolProbity: all-atom contacts and structure validation for proteins and nucleic acids , 2007 .

[9]  David Baker,et al.  Macromolecular modeling with rosetta. , 2008, Annual review of biochemistry.

[10]  Dale E Tronrud,et al.  Sorting the chaff from the wheat at the PDB , 2008, Protein science : a publication of the Protein Society.

[11]  D. Baker,et al.  RosettaHoles: Rapid assessment of protein core packing for structure prediction, refinement, design, and validation , 2008, Protein science : a publication of the Protein Society.