<html><head><meta http-equiv="Content-Type" content="text/html charset=utf-8"></head><body style="word-wrap: break-word; -webkit-nbsp-mode: space; -webkit-line-break: after-white-space;" class="">Dear Grigory,<div class=""><br class=""></div><div class="">What you are trying to do can be challenging. However, we’ve had some success determining the fold of proteins where no homologous protein structures are known by combining information from evolutionary covariance analysis with cryo-EM maps at ~6 Å resolution. Have a look at these two examples:</div><div class=""><a href="http://www.ncbi.nlm.nih.gov/pubmed/26951669" class="">http://www.ncbi.nlm.nih.gov/pubmed/26951669</a></div><div class=""><a href="http://www.ncbi.nlm.nih.gov/pubmed/26439008" class="">http://www.ncbi.nlm.nih.gov/pubmed/26439008</a></div><div class=""><br class=""></div><div class="">For these two manuscripts (3 structures), Daniel Schep built the models manually and obtained evolutionary covariance (aka "evolutionary couplings") information from Deborah Marks’ program EVcouplings (<a href="http://evfold.org/evfold-web/newmarkec.do" class="">http://evfold.org/evfold-web/newmarkec.do</a>). Evolutionary covariance analysis works best when a large multiple sequence alignment for your protein of interest can be prepared. For example, for the bovine mitochondrial ATP synthase a subunit, where >20,000 sequences are available because of homology to bacterial ATP synthases, constraints on the fold from intra-chain contacts could be detected with excellent signal to noise. For the Thermus thermophilus and Saccharomyces cerevisiae V/A- and V-ATPases, only ~3000k sequences were available (eukaryotes, archaea, and a few eubacteria) and patterns of constraints were noisier but still easily detectable.</div><div class=""><br class=""></div><div class="">Best wises,</div><div class="">John</div><div class=""><br class=""><div class="">
<div class=""><div class="">-- </div><div class="">John Rubinstein</div><div class="">Molecular Structure and Function Program</div><div class="">The Hospital for Sick Children Research Institute</div><div class="">686 Bay Street, Rm. 20-9705</div><div class="">Toronto, ON</div><div class="">Canada</div><div class="">M5G 0A4</div><div class="">Tel: (+001) 416-813-7255</div><div class="">Fax: (+001) 416-813-5022</div><div class=""><a href="http://www.sickkids.ca/research/rubinstein" class="">www.sickkids.ca/research/rubinstein</a></div></div>
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<br class=""><div><blockquote type="cite" class=""><div class="">On May 23, 2016, at 12:16 PM, Grigory Sharov <<a href="mailto:sharov.grigory@gmail.com" class="">sharov.grigory@GMAIL.COM</a>> wrote:</div><br class="Apple-interchange-newline"><div class=""><div dir="ltr" class=""><div class="">Dear all,</div><div class=""><br class=""></div><div class="">I'm looking for a software tool for <i class="">de novo</i> model building (no homologous structures available) based on a medium resolution density maps (5-8 A). The idea is to get at least a C-alpha trace and map it onto known protein sequence. </div><div class=""><br class=""></div><div class="">So far I tried Gorgon and e2pathwalker from EMAN2 without much luck and now looking into Rosetta (not sure it is suitable for my resolution). I wonder what other people are using for such task.</div><div class=""><br class=""></div><div class=""><div class=""><div dir="ltr" class=""><div class=""><div dir="ltr" class=""><div class=""><div dir="ltr" class=""><div class=""><div dir="ltr" class=""><div class=""><div dir="ltr" class=""><div class=""><div dir="ltr" class=""><div style="" class=""><font face="arial, helvetica, sans-serif" size="2" class=""><span style="font-size:10pt" class=""><br class=""></span></font></div><div style="" class=""><font face="arial, helvetica, sans-serif" size="2" class=""><span style="font-size:10pt" class="">Best regards,<br class="">Grigory</span></font></div><div style="" class=""><font face="arial, helvetica, sans-serif" size="2" class=""><span style="font-size:10pt" class=""><br class=""></span></font></div><div style="" class=""><font face="arial, helvetica, sans-serif" size="2" class=""><span style="font-size:10pt" class="">--------------------------------------------------------------------------------</span></font></div><div style="" class=""><font face="arial, helvetica, sans-serif" size="2" class=""><span style="font-size:10pt" class="">Grigory Sharov, Ph.D.</span></font></div><div style="" class=""><font face="arial, helvetica, sans-serif" size="2" class=""><span style="font-size:10pt" class="">Institute of Genetics and Molecular and Cellular Biology<br class="">Integrated Structural Biology Department (CBI)<br class="">1, rue Laurent Fries<br class="">67404 Illkirch, France</span></font></div><div style="" class=""><span style="font-size:10pt;font-family:arial,helvetica,sans-serif" class="">tel. <a href="tel:03%2069%2048%2051%2000" value="+33369485100" target="_blank" class="">03 69 48 51 00</a> </span><br class=""></div><div style="" class=""><font face="arial, helvetica, sans-serif" size="2" class=""><span style="font-size:10pt" class="">e-mail: <a href="mailto:sharov@igbmc.fr" target="_blank" class="">sharov@igbmc.fr</a></span></font></div></div></div></div></div></div></div></div></div></div></div></div></div></div>
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