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<front>
<journal-meta>
<journal-id journal-id-type="doi">10.1002/(ISSN)1097-0134</journal-id>
<journal-id journal-id-type="publisher-id">PROT</journal-id>
<journal-title-group>
<journal-title xml:lang="en">Proteins: Structure, Function, and Bioinformatics</journal-title>
<abbrev-journal-title abbrev-type="publisher" xml:lang="en">Proteins</abbrev-journal-title>
</journal-title-group>
<issn publication-format="ppub">0887-3585</issn>
<issn publication-format="epub">1097-0134</issn>
<publisher>
<publisher-name>John Wiley &amp; Sons, Inc.</publisher-name>
<publisher-loc>Hoboken, USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.1002/prot.26214</article-id>
<article-id pub-id-type="publisher-id">PROT26214</article-id>
<article-categories>
<subj-group subj-group-type="overline" xml:lang="en">
<subject>RESEARCH ARTICLE</subject>
</subj-group>
<subj-group subj-group-type="heading" xml:lang="en">
<subject>RESEARCH ARTICLES</subject>
</subj-group>
</article-categories>
<title-group>
<article-title xml:lang="en">Assessing the utility of <styled-content style="fixed-case" toggle="no">CASP14</styled-content> models for molecular replacement</article-title>
<alt-title alt-title-type="left-running-head">Millán et al.</alt-title>
</title-group>
<contrib-group>
<contrib id="prot26214-cr-0001" contrib-type="author">
<name>
<surname>Millán</surname>
<given-names>Claudia</given-names>
</name>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9283-2220</contrib-id>
<xref ref-type="aff" rid="prot26214-aff-0001">
<sup>1</sup>
</xref>
</contrib>
<contrib id="prot26214-cr-0002" contrib-type="author">
<name>
<surname>Keegan</surname>
<given-names>Ronan M.</given-names>
</name>
<xref ref-type="aff" rid="prot26214-aff-0002">
<sup>2</sup>
</xref>
</contrib>
<contrib id="prot26214-cr-0003" contrib-type="author">
<name>
<surname>Pereira</surname>
<given-names>Joana</given-names>
</name>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5588-6588</contrib-id>
<xref ref-type="aff" rid="prot26214-aff-0003">
<sup>3</sup>
</xref>
<xref ref-type="aff" rid="prot26214-aff-0004">
<sup>4</sup>
</xref>
</contrib>
<contrib id="prot26214-cr-0004" contrib-type="author">
<name>
<surname>Sammito</surname>
<given-names>Massimo D.</given-names>
</name>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8346-9247</contrib-id>
<xref ref-type="aff" rid="prot26214-aff-0001">
<sup>1</sup>
</xref>
</contrib>
<contrib id="prot26214-cr-0005" contrib-type="author">
<name>
<surname>Simpkin</surname>
<given-names>Adam J.</given-names>
</name>
<xref ref-type="aff" rid="prot26214-aff-0005">
<sup>5</sup>
</xref>
</contrib>
<contrib id="prot26214-cr-0006" contrib-type="author">
<name>
<surname>McCoy</surname>
<given-names>Airlie J.</given-names>
</name>
<xref ref-type="aff" rid="prot26214-aff-0001">
<sup>1</sup>
</xref>
</contrib>
<contrib id="prot26214-cr-0007" contrib-type="author">
<name>
<surname>Lupas</surname>
<given-names>Andrei N.</given-names>
</name>
<xref ref-type="aff" rid="prot26214-aff-0003">
<sup>3</sup>
</xref>
</contrib>
<contrib id="prot26214-cr-0008" contrib-type="author">
<name>
<surname>Hartmann</surname>
<given-names>Marcus D.</given-names>
</name>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6937-5677</contrib-id>
<xref ref-type="aff" rid="prot26214-aff-0003">
<sup>3</sup>
</xref>
</contrib>
<contrib id="prot26214-cr-0009" contrib-type="author">
<name>
<surname>Rigden</surname>
<given-names>Daniel J.</given-names>
</name>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7565-8937</contrib-id>
<xref ref-type="aff" rid="prot26214-aff-0005">
<sup>5</sup>
</xref>
</contrib>
<contrib id="prot26214-cr-0010" contrib-type="author" corresp="yes">
<name>
<surname>Read</surname>
<given-names>Randy J.</given-names>
</name>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8273-0047</contrib-id>
<email>rjr27@cam.ac.uk</email>
<xref ref-type="corresp" rid="correspondenceTo">*</xref>
<xref ref-type="aff" rid="prot26214-aff-0001">
<sup>1</sup>
</xref>
</contrib>
</contrib-group>
<aff id="prot26214-aff-0001">
<label>
<sup>1</sup>
</label>

<named-content content-type="organisation-division">Department of Haematology</named-content>

<institution>University of Cambridge, Cambridge Institute for Medical Research</institution>

<city>Cambridge</city>
 <country country="GB">UK</country>

</aff>
<aff id="prot26214-aff-0002">
<label>
<sup>2</sup>
</label>

<named-content content-type="organisation-division">Department of Scientific Computing, Science and Technologies Facilities Council</named-content>

<institution>UK Research and Innovation</institution>

<city>Oxfordshire</city>
 <named-content content-type="country-part">Didcot</named-content>
 <country country="GB">UK</country>

</aff>
<aff id="prot26214-aff-0003">
<label>
<sup>3</sup>
</label>

<institution>Max Planck Institute for Developmental Biology</institution>

<city>Tübingen</city>
 <country country="DE">Germany</country>

</aff>
<aff id="prot26214-aff-0004">
<label>
<sup>4</sup>
</label>

<named-content content-type="organisation-division">Biozentrum</named-content>

<institution>University of Basel</institution>

<city>Basel</city>
 <country country="CH">Switzerland</country>

</aff>
<aff id="prot26214-aff-0005">
<label>
<sup>5</sup>
</label>

<named-content content-type="organisation-division">Institute of Systems</named-content>

<institution>Molecular and Integrative Biology</institution>

<city>Liverpool</city>
 <country country="GB">UK</country>

</aff>
<author-notes>
<corresp id="correspondenceTo"><label>*</label>

<bold>Correspondence</bold><break/>
Randy J. Read, Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, The Keith Peters Building, Hills Road, Cambridge, CB2 0XY, UK.<break/>
Email: <email>rjr27@cam.ac.uk</email>
<break/>

</corresp>
</author-notes>
<pub-date date-type="pub" publication-format="electronic"><day>21</day>
<month>08</month>
<year>2021</year>
</pub-date><fpage/><lpage/><history>

<date date-type="rev-recd">
<day>20</day>
<month>07</month>
<year>2021</year>
</date>

<date date-type="received">
<day>18</day>
<month>06</month>
<year>2021</year>
</date>

<date date-type="accepted">
<day>27</day>
<month>07</month>
<year>2021</year>
</date>

</history>
<permissions>
<copyright-statement content-type="issue-copyright">© 2021 Wiley Periodicals LLC.</copyright-statement>
<copyright-statement content-type="article-copyright">© 2021 The Authors. <italic>Proteins: Structure, Function, and Bioinformatics</italic> published by Wiley Periodicals LLC.</copyright-statement>
<copyright-year>2021</copyright-year>
<copyright-holder>© 2021 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.</copyright-holder>
<license>
<ali:license_ref>http://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This is an open access article under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution</ext-link> License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<abstract xml:lang="en" abstract-type="main">
<title>Abstract</title>
<p xml:lang="en">The assessment of CASP models for utility in molecular replacement is a measure of their use in a valuable real‐world application. In CASP7, the metric for molecular replacement assessment involved full likelihood‐based molecular replacement searches; however, this restricted the assessable targets to crystal structures with only one copy of the target in the asymmetric unit, and to those where the search found the correct pose. In CASP10, full molecular replacement searches were replaced by likelihood‐based rigid‐body refinement of models superimposed on the target using the LGA algorithm, with the metric being the refined log‐likelihood‐gain (LLG) score. This enabled multi‐copy targets and very poor models to be evaluated, but a significant further issue remained: the requirement of diffraction data for assessment. We introduce here the relative‐expected‐LLG (reLLG), which is independent of diffraction data. This reLLG is also independent of any crystal form, and can be calculated regardless of the source of the target, be it X‐ray, NMR or cryo‐EM. We calibrate the reLLG against the LLG for targets in CASP14, showing that it is a robust measure of both model and group ranking. Like the LLG, the reLLG shows that accurate coordinate error estimates add substantial value to predicted models. We find that refinement by CASP groups can often convert an inadequate initial model into a successful MR search model. Consistent with findings from others, we show that the AlphaFold2 models are sufficiently good, and reliably so, to surpass other current model generation strategies for attempting molecular replacement phasing.</p>
</abstract>
<kwd-group kwd-group-type="author-generated" xml:lang="en">
<kwd id="prot26214-kwd-0001">CASP</kwd>
<kwd id="prot26214-kwd-0002">likelihood</kwd>
<kwd id="prot26214-kwd-0003">model refinement</kwd>
<kwd id="prot26214-kwd-0004">molecular replacement</kwd>
<kwd id="prot26214-kwd-0005">structure prediction</kwd>
</kwd-group>
<funding-group>
<award-group id="funding-0001">
<funding-source>

<institution-wrap>
<institution>CCP4</institution>
</institution-wrap>

</funding-source>
</award-group>
</funding-group>
<funding-group>
<award-group id="funding-0002">
<funding-source>

<institution-wrap>
<institution>Max‐Planck‐Gesellschaft</institution>
<institution-id>http://dx.doi.org/10.13039/501100004189</institution-id>
</institution-wrap>

</funding-source>
</award-group>
</funding-group>
<funding-group>
<award-group id="funding-0003">
<funding-source>

<institution-wrap>
<institution>Wellcome Trust</institution>
</institution-wrap>

</funding-source>
<award-id>209407/Z/17/Z</award-id>
</award-group>
</funding-group>
<funding-group>
<award-group id="funding-0004">
<funding-source>

<institution-wrap>
<institution>Biotechnology and Biological Sciences Research Council</institution>
<institution-id>http://dx.doi.org/10.13039/501100000268</institution-id>
</institution-wrap>

</funding-source>
<award-id>BB/S007105/1</award-id>
</award-group>
</funding-group>
<counts>
<fig-count count="12"/>
<table-count count="2"/>
<page-count count="18"/>
<word-count count="10833"/>
</counts>
</article-meta>
</front>
</article>