title: De Novo modeling in cryo-EM density maps with Pathwalking.
abstract: As electron cryo-microscopy (cryo-EM) can now frequently achieve near atomic resolution, accurate interpretation of these density maps in terms of atomistic detail has become paramount in deciphering macromolecular structure and function. However, there are few software tools for modeling protein structure from cryo-EM density maps in this resolution range. Here, we present an extension of our original Pathwalking protocol, which can automatically trace a protein backbone directly from a near-atomic resolution (3-6Å) density map. The original Pathwalking approach utilized a Traveling Salesman Problem solver for backbone tracing, but manual adjustment was still required during modeling. In the new version, human intervention is minimized and we provide a more robust approach for backbone modeling. This includes iterative secondary structure identification, termini detection and the ability to model multiple subunits without prior segmentation. Overall, the new Pathwalking procedure provides a more complete and robust tool for annotating protein structure function in near-atomic resolution density maps.
authors.affiliation: Program in Structural and Computational Biology and Molecular Biophysics, United States; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, United States.
authors.forename: Muyuan
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Psychology, United States; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, United States.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Baldwin
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, United States.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Ludtke
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, United States. Electronic address: mbaker@bcm.edu.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Baker
mesh_terms: D000465:Algorithms; D020285:Cryoelectron Microscopy / Q000379:methods*; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000648:ultrastructure*; D012984:Software
chemical_list: D011506:Proteins
keywords: Backbone model; Protein structure