Protein Structure Fitting and Refinement Guided by Cryo-EM Density

Maya Topf, Keren Lasker, Ben Webb, Haim Wolfson, Wah Chiu, Andrej Sali

Research output: Contribution to journalArticlepeer-review

Abstract

For many macromolecular assemblies, both a cryo-electron microscopy map and atomic structures of its component proteins are available. Here we describe a method for fitting and refining a component structure within its map at intermediate resolution (<15 Å). The atomic positions are optimized with respect to a scoring function that includes the crosscorrelation coefficient between the structure and the map as well as stereochemical and nonbonded interaction terms. A heuristic optimization that relies on a Monte Carlo search, a conjugate-gradients minimization, and simulated annealing molecular dynamics is applied to a series of subdivisions of the structure into progressively smaller rigid bodies. The method was tested on 15 proteins of known structure with 13 simulated maps and 3 experimentally determined maps. At ∼10 Å resolution, Cα rmsd between the initial and final structures was reduced on average by ∼53%. The method is automated and can refine both experimental and predicted atomic structures.

Original languageEnglish
Pages (from-to)295-307
Number of pages13
JournalStructure
Volume16
Issue number2
DOIs
StatePublished - 12 Feb 2008

Keywords

  • PROTEINS

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