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On the complexity of Engh and Huber refinement restraints: the angle ? as example.

ABSTRACT: The Engh and Huber parameters for bond lengths and bond angles have been used uncontested in macromolecular structure refinement from 1991 until very recently, despite critical discussion of their ubiquitous validity by many authors. An extensive analysis of the backbone angle ? (N-C(?)-C) illustrates that the Engh and Huber parameters can indeed be improved and a recent study [Tronrud et al. (2010), Acta Cryst. D66, 834-842] confirms these ideas. However, the present study of ? shows that improving the Engh and Huber parameters will be considerably more complex than simply making the parameters a function of the backbone ?, ? angles. Many other aspects, such as the cooperativity of hydrogen bonds, the bending of secondary-structure elements and a series of biophysical aspects of the 20 amino-acid types, will also need to be taken into account. Different sets of Engh and Huber parameters will be needed for conceptually different refinement programs.

SUBMITTER: Touw WG

PROVIDER: S-EPMC2995724 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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On the complexity of Engh and Huber refinement restraints: the angle τ as example.

Touw Wouter G WG Vriend Gert G

Acta crystallographica. Section D, Biological crystallography 20101116 Pt 12

The Engh and Huber parameters for bond lengths and bond angles have been used uncontested in macromolecular structure refinement from 1991 until very recently, despite critical discussion of their ubiquitous validity by many authors. An extensive analysis of the backbone angle τ (N-C(α)-C) illustrates that the Engh and Huber parameters can indeed be improved and a recent study [Tronrud et al. (2010), Acta Cryst. D66, 834-842] confirms these ideas. However, the present study of τ shows that impro ...[more]

PMID: 21123875

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Project description:Cryo-EM has become one of the prime methods for protein structure elucidation, frequently yielding density maps with near-atomic or medium resolution. If protein structures cannot be deduced unambiguously from the density maps, computational structure refinement tools are needed to generate protein structural models. We have previously developed an iterative Rosetta-MDFF protocol that used cryo-EM densities to refine protein structures. Here we show that, in addition to cryo-EM densities, incorporation of other experimental restraints into the Rosetta-MDFF protocol further improved refined structures. We used NMR chemical shift (CS) data integrated with cryo-EM densities in our hybrid protocol in both the Rosetta step and the molecular dynamics (MD) simulations step. In 15 out of 18 cases for all MD rounds, the refinement results obtained when density maps and NMR chemical shift data were used in combination outperformed those of density map-only refinement. Notably, the improvement in refinement was highest when medium and low-resolution density maps were used. With our hybrid method, the RMSDs of final models obtained were always better than the RMSDs obtained by our previous protocol with just density refinement for both medium (6.9 Å) and low (9 Å) resolution maps. For all the six test proteins with medium resolution density maps (6.9 Å), the final refined structure RMSDs were lower for the hybrid method than for the cryo-EM only refinement. The final refined RMSDs were less than 1.5 Å when our hybrid protocol was used with 4 Å density maps. For four out of the six proteins the final RMSDs were even less than 1 Å. This study demonstrates that by using a combination of cryo-EM and NMR restraints, it is possible to refine structures to atomic resolution, outperforming single restraint refinement. This hybrid protocol will be a valuable tool when only low-resolution cryo-EM density data and NMR chemical shift data are available to refine structures.

Dataset Information

On the complexity of Engh and Huber refinement restraints: the angle ? as example.

Publications

On the complexity of Engh and Huber refinement restraints: the angle τ as example.

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