Constructing and Validating Initial Cα Models from Subnanometer Resolution Density Maps with Pathwalking

By M. R. Baker, Ian Rees, Steven J. Ludtke, Wah Chiu, Matthew L. Baker. 2012

42 citations recorded by the source corpus.

A significant number of macromolecular structures solved by electron cryo-microscopy and X-ray crystallography obtain resolutions of 3.5–6Å, at which direct atomistic interpretation is difficult. To address this, we developed pathwalking, a semi-automated protocol to enumerate reasonable Cα models from near-atomic resolution density maps without a structural template or sequence-structure correspondence. Pathwalking uses a novel approach derived from the Traveling Salesman Problem to rapidly generate an ensemble of initial models for individual proteins, which can later be optimized to produce full atomic models. Pathwalking can also be used to validate and identify potential structural ambiguities in models generated from near-atomic resolution density maps. In this work, examples from the EMDB and PDB are used to assess the broad applicability and accuracy of our method. With the growing number of near-atomic resolution density maps from cryo-EM and X-ray crystallography, pathwalking can become an important tool in modeling protein structures.

Subfields: Materials Chemistry, Molecular Biology, Structural Biology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Materials Chemistry

1. Paul D. Adams
2. Pavel V. Afonine
3. Randy J. Read
4. T. C. Terwilliger
5. T. Croll
6. Nigel W. Moriarty
7. A. McCoy
8. G. Bunkoczi

In Molecular Biology

1. Paul D. Adams
2. Randy J. Read
3. Pavel V. Afonine
4. T. C. Terwilliger
5. T. Croll
6. A. McCoy
7. Nigel W. Moriarty
8. Jane S. Richardson

In Structural Biology

1. T. Croll
2. Tom Burnley
3. S. W. Hoh
4. T. C. Terwilliger
5. Kevin Cowtan
6. Tristan Cragnolini
7. Paul D. Adams
8. Li-Wei Hung

Citations in the corpus

• Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix (2019, methodology): “Pathwalker can construct protein backbone models directly from near-atomic resolution cryo-EM density maps using a modified approach to traveling salesman problem solvers.”
• Current approaches for automated model building into cryo-EM maps using Buccaneer with CCP-EM (2020, methodology): “…(<4 Å), has motivated the modification of existing and the development of new model-building tools to interpret cryo-EM maps (Cowtan, 2008; Baker et al., 2012; Brown et al., 2015; Wang et al., 2015; Chen et al., 2016; Zhou et al., 2017; Terwilliger, Adams et al., 2018; Terashi & Kihara,…”
• Integrating model simulation tools and cryo‐electron microscopy (2022, methodology): “Pathwalking 88 is a semi-automated template-free protocol to enumerate C α models from 3.5 to 6 Å resolution density maps.”