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    P.S.: In case you want the occupancies to add up to 1, the
    constrained group will be looking like this:<br>
    <br>
    refinement {<br>
      refine {<br>
        occupancies {<br>
          constrained_group {<br>
            selection = chain A and resseq 123 and resname LIG<br>
            selection = chain B and resseq 890 and altloc A<br>
          }<br>
        }<br>
      }<br>
    }<br>
    <br>
    Note two selections in the group, meaning that occupancy of (chain A
    and resseq 123 and resname LIG) will be refined and constraied
    between 0 and 1, occupancy of (chain B and resseq 890 and altloc A)
    will be refined and constraied between 0 and 1, and occupancy of
    (chain A and resseq 123 and resname LIG) plus occupancy of (chain B
    and resseq 890 and altloc A) will be 1.<br>
    <br>
    Pavel<br>
    <br>
    <div class="moz-cite-prefix">On 3/2/18 06:59, Pavel Afonine wrote:<br>
    </div>
    <blockquote type="cite"
      cite="mid:653c5c12-904a-34fe-2f3a-ba641efc2835@lbl.gov">
      <meta http-equiv="Content-Type" content="text/html; charset=utf-8">
      Hi Jason,<br>
      <br>
      Oleg is correct, you can assign the ligand and PHE different
      non-blanc altlocs (say A and B). In this case PHE and ligand will
      not 'see' each other via repulsion term of restraints. Also, their
      occupancies will be refined independently and will be constrained
      to be within 0 and 1, but it will not make sure that they add up
      to 1. If you want them to add up to 1, then make a parameter file
      with a constrained group as described in one of examples here:<br>
      <br>
      "13 typical occupancy refinement scenarios and available options
      in phenix.refine"<br>
      <a class="moz-txt-link-freetext"
        href="http://phenix-online.org/newsletter/"
        moz-do-not-send="true">http://phenix-online.org/newsletter/</a><br>
      <br>
      You can do it in the GUI too.<br>
      <br>
      Let us know if you more questions or problems!<br>
      <br>
      Pavel<br>
      <br>
      <div class="moz-cite-prefix">On 3/2/18 02:57, Oleg Sobolev wrote:<br>
      </div>
      <blockquote type="cite"
cite="mid:CADd3otGuVs-pmOoSsTeO6kSZM91g5ZVn8YnQkFUCNdW2KNA72w@mail.gmail.com">
        <div dir="ltr">Hi Jason,
          <div><br>
          </div>
          <div class="gmail_extra">
            <div class="gmail_quote">
              <blockquote class="gmail_quote" style="margin:0 0 0
                .8ex;border-left:1px #ccc solid;padding-left:1ex">
                <div style="word-wrap:break-word">
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                    <div
                      style="margin:0px;font-size:8px;line-height:normal"><br>
                    </div>
                  </div>
                  <div>The ligand and APHE got pushed away from one
                    another and off of their respective densities.
                    Occupancies for both were reduced to 0.5 for the
                    refinement. What am I doing wrong here? Does the
                    ligand need to have an altloc as well? But I don’t
                    see an alternative conformation. </div>
                </div>
              </blockquote>
              <div><br>
              </div>
              <div>Yes, the ligand also needs an altloc, and it should
                be different from PHE altloc. This way the refinement
                will know that these atoms don't see each other. You
                don't have to put two alternative conformations for the
                ligand, you can have just one with partial occupancy
                (&lt;1.0) which will mean that the ligand is not always
                there.</div>
              <div> </div>
              <div>Best regards,</div>
              <div>Oleg Sobolev.</div>
              <blockquote class="gmail_quote" style="margin:0px 0px 0px
                0.8ex;border-left:1px solid
                rgb(204,204,204);padding-left:1ex">
                <div style="word-wrap:break-word"> <br>
                  <div>
                    <blockquote type="cite">
                      <div>On Feb 28, 2018, at 5:35 PM, van den Bedem,
                        Henry &lt;<a
                          href="mailto:vdbedem@slac.stanford.edu"
                          target="_blank" moz-do-not-send="true">vdbedem@slac.stanford.edu</a>&gt;
                        wrote:</div>
                      <br
                        class="m_8858005827093028639Apple-interchange-newline">
                      <div>
                        <div class="m_8858005827093028639WordSection1"
style="font-family:Helvetica;font-size:14px;font-style:normal;font-variant-caps:normal;font-weight:normal;letter-spacing:normal;text-align:start;text-indent:0px;text-transform:none;white-space:normal;word-spacing:0px">
                          <div style="margin:0in 0in
                            0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                            If the phe is a gatekeeper, shouldn’t the
                            ligand be refined at partial occupancy; i.e.
                            occupancies not necessarily have to ‘add up’
                            as you suggest? Maybe this link is helpful
                            too:<span
                              class="m_8858005827093028639Apple-converted-space"> </span><a
href="http://www.biorxiv.org/content/early/2018/01/24/253419"
                              style="color:rgb(149,79,114);text-decoration:underline"
                              target="_blank" moz-do-not-send="true">www.biorxiv.org/content/<wbr>early/2018/01/24/253419</a></div>
                          <div style="margin:0in 0in
                            0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                             </div>
                          <div style="margin:0in 0in
                            0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                            H</div>
                          <div style="margin:0in 0in
                            0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                             </div>
                          <div style="border-style:solid none
                            none;border-top-width:1pt;border-top-color:rgb(181,196,223);padding:3pt
                            0in 0in">
                            <div style="margin:0in 0in
                              0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                              <b><span style="font-size:12pt">From:<span
class="m_8858005827093028639Apple-converted-space"> </span></span></b><span
                                style="font-size:12pt">&lt;<a
                                  href="mailto:phenixbb-bounces@phenix-online.org"
style="color:rgb(149,79,114);text-decoration:underline" target="_blank"
                                  moz-do-not-send="true">phenixbb-bounces@<wbr>phenix-online.org</a>&gt;
                                on behalf of "Phan, Jason" &lt;<a
                                  href="mailto:jason.phan@vanderbilt.edu"
style="color:rgb(149,79,114);text-decoration:underline" target="_blank"
                                  moz-do-not-send="true">jason.phan@vanderbilt.edu</a>&gt;<br>
                                <b>Date:<span
                                    class="m_8858005827093028639Apple-converted-space"> </span></b>Wednesday,
                                February 28, 2018 at 1:30 PM<br>
                                <b>To:<span
                                    class="m_8858005827093028639Apple-converted-space"> </span></b>"<a
href="mailto:phenixbb@phenix-online.org"
                                  style="color:rgb(149,79,114);text-decoration:underline"
                                  target="_blank" moz-do-not-send="true">phenixbb@phenix-online.<wbr>org</a>"
                                &lt;<a
                                  href="mailto:phenixbb@phenix-online.org"
style="color:rgb(149,79,114);text-decoration:underline" target="_blank"
                                  moz-do-not-send="true">phenixbb@phenix-online.org</a>&gt;<br>
                                <b>Subject:<span
                                    class="m_8858005827093028639Apple-converted-space"> </span></b>[phenixbb]
                                Overlapping ligand-protein side chain
                                density</span></div>
                          </div>
                          <span class="">
                            <div>
                              <div style="margin:0in 0in
                                0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                 </div>
                            </div>
                            <div style="margin:0in 0in
                              0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                              <a
                                name="m_8858005827093028639__MailOriginalBody"
                                moz-do-not-send="true">All, <span
                                  class="m_8858005827093028639Apple-converted-space"> </span></a></div>
                            <div>
                              <div style="margin:0in 0in
                                0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                <span> </span></div>
                            </div>
                            <div>
                              <div style="margin:0in 0in
                                0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                <span>A piece of a ligand and the side
                                  chain of a “gate-keeper” Phe occupy
                                  the same space with well-defined
                                  features observed for both (resolution
                                  is 1.7 A). It looks about 50:50. How
                                  do you refine both ligand and protein
                                  side chain in this case? A couple of
                                  phenixbb suggestions for dealing with
                                  ligand-ligand overlapping density have
                                  been considered. With the first
                                  suggestion, the two entities still
                                  clashed and moved apart off of their
                                  respective densities. The second
                                  suggestion is not applicable in this
                                  case since the other molecule is not a
                                  ligand but part of the protein but it
                                  was tested anyway. Although there was
                                  no bumping, the occupancies don’t add
                                  up, resulting in a big blob of
                                  negative density around the ligand
                                  piece. </span></div>
                            </div>
                            <div>
                              <div style="margin:0in 0in
                                0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                <span> </span></div>
                            </div>
                            <div>
                              <div style="margin:0in 0in
                                0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                <span>------------------------------</span></div>
                            </div>
                            <div>
                              <div>
                                <div style="margin:0in 0in
                                  0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                  <span>Only two comments:</span></div>
                              </div>
                              <div>
                                <div style="margin:0in 0in
                                  0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                  <span> </span></div>
                              </div>
                              <ol start="1"
                                style="margin-bottom:0in;margin-top:0in"
                                type="a">
                                <li class="MsoNormal" style="margin:0in
                                  0in
                                  0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                  <span>At that resolution, constrained
                                    group occupancy refinement should
                                    work reasonably well (provided you
                                    can model the 2 entities). Then you
                                    also do not have clashes between the
                                    molecules, because Occ(A)+Occ(B)=1,
                                    meaning when one (A) is there, the
                                    other one (B) is not. This works
                                    with refmac (external keyword file);
                                    if you need more sophisticated
                                    occupancy re/constraints SHELXL may
                                    offer more opportunities.</span></li>
                                <li class="MsoNormal" style="margin:0in
                                  0in
                                  0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                  <span>There is no necessity for the
                                    two NCS copies of the binding site
                                    to look exactly the same
                                    (non-equivalent). Maybe there is a
                                    good reason/story (accessibility,
                                    contacts etc) for one site to be
                                    occupied differently than the other
                                    one. </span></li>
                              </ol>
                              <div>
                                <div style="margin:0in 0in
                                  0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                  <span> </span></div>
                              </div>
                              <div>
                                <div style="margin:0in 0in
                                  0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                  <span>Best, BR</span></div>
                              </div>
                            </div>
                            <div>
                              <div style="margin:0in 0in
                                0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                <span>——————————————</span></div>
                            </div>
                            <div>
                              <div>
                                <div style="margin:0in 0in
                                  0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                  <span><span
                                      style="font-size:10.5pt;font-family:Helvetica">Modeling
                                      two molecules that occupy
                                      overlapping binding sites in a
                                      structure simply involves
                                      designating them as alternate
                                      conformers, with the same chain
                                      and residue number, and an
                                      occupancy that sums to 1.0. For
                                      example, if you have an AMP and an
                                      ADP that occupy the same binding
                                      site, you would define them as</span></span></div>
                              </div>
                              <div>
                                <div style="margin:0in 0in
                                  0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                  <span><span
                                      style="font-size:10.5pt;font-family:Helvetica"> </span></span></div>
                              </div>
                              <div>
                                <div>
                                  <div style="margin:0in 0in
                                    0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                    <span><span
                                        style="font-size:10.5pt;font-family:Courier">AAMP
                                        B 501</span></span><span><span
                                        style="font-size:10.5pt;font-family:Helvetica"></span></span></div>
                                </div>
                                <div>
                                  <div style="margin:0in 0in
                                    0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                    <span><span
                                        style="font-size:10.5pt;font-family:Courier">BADP
                                        B 501</span></span><span><span
                                        style="font-size:10.5pt;font-family:Helvetica"></span></span></div>
                                </div>
                              </div>
                              <div>
                                <div style="margin:0in 0in
                                  0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                  <span><span
                                      style="font-size:10.5pt;font-family:Helvetica"> </span></span></div>
                              </div>
                              <div>
                                <div style="margin:0in 0in
                                  0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                  <span><span
                                      style="font-size:10.5pt;font-family:Helvetica">and
                                      initially set the occupancies for
                                      the atoms in each conformer to the
                                      ratio (50:50, 30:70, etc.) that
                                      you observe in the density.</span></span></div>
                              </div>
                              <div>
                                <div style="margin:0in 0in
                                  0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                  <span><span
                                      style="font-size:10.5pt;font-family:Helvetica"> </span></span></div>
                              </div>
                              <div>
                                <div style="margin:0in 0in
                                  0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                  <span><span
                                      style="font-size:10.5pt;font-family:Helvetica">Refinement
                                      in this manner is straightforward
                                      in PHENIX.</span></span></div>
                              </div>
                              <div>
                                <div style="margin:0in 0in
                                  0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                  <span><span
                                      style="font-size:10.5pt;font-family:Helvetica"> </span></span></div>
                              </div>
                              <div>
                                <div style="margin:0in 0in
                                  0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                  <span><span
                                      style="font-size:10.5pt;font-family:Helvetica">Diana</span></span></div>
                              </div>
                              <div>
                                <div style="margin:0in 0in
                                  0.0001pt;font-size:11pt;font-family:Calibri,sans-serif">
                                  <span><span
                                      style="font-size:10.5pt;font-family:Helvetica">----------------------------</span></span></div>
                              </div>
                            </div>
                          </span></div>
                      </div>
                    </blockquote>
                  </div>
                  <br>
                </div>
                <br>
                ______________________________<wbr>_________________<br>
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            <br>
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        <br>
        <pre wrap="">_______________________________________________
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