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<div style="line-height:1.38; margin-top:0pt; margin-bottom:0pt" class=""><font face="Arial" style="font-size:14px" class=""><span style="white-space:pre-wrap" class="">Dear All,</span></font></div>
<div style="line-height:1.38; margin-top:0pt; margin-bottom:0pt" class=""><font face="Arial" style="font-size:14px" class=""><span style="white-space:pre-wrap" class=""><br class="">
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<div style="line-height:1.38; margin-top:0pt; margin-bottom:0pt" class=""><font face="Arial" style="font-size:14px" class=""><span style="white-space:pre-wrap" class="">We are happy to announce the first release of the CoVal database (<a href="https://urldefense.com/v3/__https://coval.ccpem.ac.uk/__;!!Mih3wA!V8bym00oPyjOoTwpVcc0NrhoRysNwGQsJItKBy3ZYhAYTCnYVgHzLok28jIO1IfLoA$" target="_BLANK" class="">https://coval.ccpem.ac.uk</a>).
</span><span style="white-space:pre-wrap; font-variant-ligatures:normal; font-variant-east-asian:normal; vertical-align:baseline" class="">CoVal is a database designed to identify amino acid replacement mutations from the genomes of SARS-CoV2 virus and map
 them onto 3D atomic models derived from cryo-EM data. The database is updated bi-weekly with new genome sequences from GISAID (<a href="https://urldefense.com/v3/__https://www.gisaid.org/__;!!Mih3wA!V8bym00oPyjOoTwpVcc0NrhoRysNwGQsJItKBy3ZYhAYTCnYVgHzLok28jKn1dfNGA$" class="">https://www.gisaid.org/</a>) and new depositions from PDB/EMDB. In the present release,</span><span style="white-space:pre-wrap; background-color:rgb(255,255,255); font-variant-ligatures:normal; font-variant-east-asian:normal; vertical-align:baseline" class="">11838
 amino acid replacement mutations </span><span style="background-color:rgb(255,255,255); font-variant-ligatures:normal; font-variant-east-asian:normal; vertical-align:baseline; white-space:pre-wrap" class="">from 190696 genome sequences from
</span><span style="font-variant-ligatures:normal; font-variant-east-asian:normal; vertical-align:baseline; white-space:pre-wrap" class="">GISAID (</span><a href="https://urldefense.com/v3/__https://www.gisaid.org/__;!!Mih3wA!V8bym00oPyjOoTwpVcc0NrhoRysNwGQsJItKBy3ZYhAYTCnYVgHzLok28jKn1dfNGA$" style="text-decoration:none" target="_BLANK" class=""><span style="color:rgb(0,0,0); font-variant-ligatures:normal; font-variant-east-asian:normal; text-decoration:underline; vertical-align:baseline; white-space:pre-wrap" class="">https://www.gisaid.org/</span></a><span style="font-variant-ligatures:normal; font-variant-east-asian:normal; vertical-align:baseline; white-space:pre-wrap" class="">)
 are included</span><span style="background-color:rgb(255,255,255); font-variant-ligatures:normal; font-variant-east-asian:normal; vertical-align:baseline; white-space:pre-wrap" class="">.</span><span style="white-space:pre-wrap; background-color:rgb(255,255,255)" class="">The</span><span style="background-color:rgb(255,255,255); font-variant-ligatures:normal; font-variant-east-asian:normal; vertical-align:baseline; white-space:pre-wrap" class="">
 database also </span><span style="font-variant-ligatures:normal; font-variant-east-asian:normal; vertical-align:baseline; white-space:pre-wrap" class="">provides details on the demographic distribution of mutations and mapping the identified
</span><span style="white-space:pre-wrap" class="">mutations onto the three-dimensional structures of proteins in various biological forms, determined experimentally using cryo-EM. </span></font><span style="font-family:Arial; font-size:14px; white-space:pre-wrap" class="">CoVal
 is under active development and testing, and more features will be added in near future. The service will also be made available</span><span style="font-family:Arial; font-size:14px; white-space:pre-wrap" class=""> via CCP4-online:
</span><span style="font-family:Arial; font-size:14px; white-space:pre-wrap" class=""><a href="https://urldefense.com/v3/__https://ccp4online.ccp4.ac.uk/ccp4online/__;!!Mih3wA!V8bym00oPyjOoTwpVcc0NrhoRysNwGQsJItKBy3ZYhAYTCnYVgHzLok28jJH5nYI3Q$" class="">https://ccp4online.ccp4.ac.uk/ccp4online/</a></span><span style="font-family:Arial; font-size:14px; white-space:pre-wrap" class="">.</span><span style="font-family:Arial; font-size:14px; white-space:pre-wrap" class="">
</span></div>
<div style="line-height:1.38; margin-top:0pt; margin-bottom:0pt" class=""><span style="font-family: Arial; font-size: 14px; white-space: pre-wrap;" class=""><br class="">
</span></div>
<div style="line-height:1.38; margin-top:0pt; margin-bottom:0pt" class=""><span style="font-family: Arial; font-size: 14px; white-space: pre-wrap;" class="">One of the main aims behind development of this database is to provide various validation scores for
 global quality</span><span style="font-size: 14px; font-family: Arial; white-space: pre-wrap;" class=""> of
</span><span style="font-size: 14px; font-family: Arial; font-variant-ligatures: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;" class="">the atomic models, and the local quality of mutation site(s) and the structural
 neighbors.</span><span style="font-size: 14px; font-family: Arial; font-variant-ligatures: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;" class=""> This is highlighted using different</span><span style="white-space: pre-wrap; font-size: 14px; font-family: Arial;" class="">
 quality indicators that are part of the CCP-EM software suite. We hope this service hosted by CCP-EM (STFC) is timely and beneficial to understand</span><span style="font-family: Arial; font-size: 14px; white-space: pre-wrap;" class=""> the impacts of mutations
 on protein structure and function, and also addresses the need of validation of cryo-EM</span><span style="font-size: 14px; font-family: Arial; font-variant-ligatures: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;" class="">
 derived structures. </span><span style="font-size: 14px; font-family: Arial; font-variant-ligatures: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;" class="">We plan to extend the database with structures derived
 from X-ray crystallography</span><span style="font-size: 14px; font-family: Arial; font-variant-ligatures: normal; font-variant-east-asian: normal; vertical-align: baseline; white-space: pre-wrap;" class=""> and also include insights
</span><span style="white-space: pre-wrap; font-size: 14px; font-family: Arial;" class="">on selected mutations based on molecular dynamics studies. </span></div>
<div style="line-height:1.38; margin-top:0pt; margin-bottom:0pt" class=""><span style="font-family:Arial; font-size:14px; white-space:pre-wrap" class=""></span></div>
<div style="line-height:1.38; margin-top:0pt; margin-bottom:0pt" class=""><span style="font-family:Arial; font-size:14px; white-space:pre-wrap" class="">We hope the community will benefit from the resource and in case of any questions, please contact us for</span><span style="font-family:Arial; font-size:14px; white-space:pre-wrap" class="">
 more details. </span></div>
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