For higher-resolution structures, it is possible to build the macromolecule directly, without prior structural knowledge from other methods. Computer algorithms have also been developed for this task.<ref>{{citation |last1=Jamali |first1=Kiarash |last2=Käll |first2=Lukas |last3=Zhang |first3=Rui |last4=Brown |first4=Alan |last5=Kimanius |first5=Dari |last6=Scheres |first6=Sjors H.W. |title=Automated model building and protein identification in cryo-EM maps |journal=BioRxiv: The Preprint Server for Biology |date=16 May 2023 |pages=2023.05.16.541002 |doi=10.1101/2023.05.16.541002|pmid=37292681 |pmc=10245678 }}</ref>
As high-resolution cyrocryo-EM models are relative new, quality control tools are not as plentiful as it is for X-ray models. Nevertheless, cyrocryo-EM ("real space") versions of the [[difference density map]],<ref>{{cite journal |last1=Yamashita |first1=Keitaro |last2=Palmer |first2=Colin M. |last3=Burnley |first3=Tom |last4=Murshudov |first4=Garib N. |title=Cryo-EM single-particle structure refinement and map calculation using Servalcat |journal=Acta Crystallographica Section D Structural Biology |date=1 October 2021 |volume=77 |issue=10 |pages=1282–1291 |doi=10.1107/S2059798321009475 |pmid=34605431 |pmc=8489229 |bibcode=2021AcCrD..77.1282Y |doi-access=free |quote=}}</ref> cross-validation using a "free" map (comparable to the use of a free [[R-factor]]),<ref>{{cite journal |last1=Falkner |first1=B |last2=Schröder |first2=GF |title=Cross-validation in cryo-EM-based structural modeling. |journal=Proceedings of the National Academy of Sciences of the United States of America |date=28 May 2013 |volume=110 |issue=22 |pages=8930–5 |doi=10.1073/pnas.1119041110 |pmid=23674685|pmc=3670386 |bibcode=2013PNAS..110.8930F |doi-access=free }}</ref><ref>{{cite journal |last1=Beckers |first1=Maximilian |last2=Mann |first2=Daniel |last3=Sachse |first3=Carsten |title=Structural interpretation of cryo-EM image reconstructions |journal=Progress in Biophysics and Molecular Biology |date=March 2021 |volume=160 |pages=26–36 |doi=10.1016/j.pbiomolbio.2020.07.004 |pmid=32735944 |doi-access=free}}</ref> and various [[structure validation]] tools have began to appear.
