Fitting low-resolution cryo-EM maps of proteins using constrained geometric simulations

C.C. Jolley, S. Wells, P. Fromme, M.F. Thorpe

Research output: Contribution to journalArticlepeer-review

68 Citations (SciVal)


Recent experimental advances in producing density maps from cryo-electron microscopy (cryo-EM) have challenged theorists to develop improved techniques to provide structural models that are consistent with the data and that preserve all the local stereochemistry associated with the biomolecule. We develop a new technique that maintains the local geometry and chemistry at each stage of the fitting procedure. A geometric simulation is used to drive the structure from some appropriate starting point (a nearby experimental structure or a modeled structure) toward the experimental density, via a set of small incremental motions. Structural motifs such as α-helices can be held rigid during the fitting procedure as the starting structure is brought into alignment with the experimental density. After validating this procedure on simulated data for adenylate kinase and lactoferrin, we show how cryo-EM data for two different GroEL structures can be fit using a starting x-ray crystal structure. We show that by incorporating the correct local stereochemistry in the modeling, structures can be obtained with effective resolution that is significantly higher than might be expected from the nominal cryo-EM resolution.
Original languageEnglish
Pages (from-to)1613-1621
Number of pages9
JournalBiophysical Journal
Issue number5
Publication statusPublished - 1 Mar 2008


Dive into the research topics of 'Fitting low-resolution cryo-EM maps of proteins using constrained geometric simulations'. Together they form a unique fingerprint.

Cite this