title: Constructing and validating initial Cα models from subnanometer resolution density maps with pathwalking.
abstract: 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 an 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.
authors.affiliation: National Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Mariah R
authors.initials: MR
authors.lastname: Baker
authors.forename: Ian
authors.initials: I
authors.lastname: Rees
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Ludtke
authors.forename: Wah
authors.initials: W
authors.lastname: Chiu
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Baker
mesh_terms: D000465:Algorithms; D020285:Cryoelectron Microscopy / Q000379:methods; D018360:Crystallography, X-Ray / Q000379:methods; D046911:Macromolecular Substances / Q000737:chemistry*; D008958:Models, Molecular; D008967:Molecular Biology / Q000379:methods*; D017510:Protein Folding; D012984:Software
chemical_list: D046911:Macromolecular Substances