<html xmlns:v="urn:schemas-microsoft-com:vml" xmlns:o="urn:schemas-microsoft-com:office:office" xmlns:w="urn:schemas-microsoft-com:office:word" xmlns:x="urn:schemas-microsoft-com:office:excel" xmlns:p="urn:schemas-microsoft-com:office:powerpoint" xmlns:a="urn:schemas-microsoft-com:office:access" xmlns:dt="uuid:C2F41010-65B3-11d1-A29F-00AA00C14882" xmlns:s="uuid:BDC6E3F0-6DA3-11d1-A2A3-00AA00C14882" xmlns:rs="urn:schemas-microsoft-com:rowset" xmlns:z="#RowsetSchema" xmlns:b="urn:schemas-microsoft-com:office:publisher" xmlns:ss="urn:schemas-microsoft-com:office:spreadsheet" xmlns:c="urn:schemas-microsoft-com:office:component:spreadsheet" xmlns:odc="urn:schemas-microsoft-com:office:odc" xmlns:oa="urn:schemas-microsoft-com:office:activation" xmlns:html="http://www.w3.org/TR/REC-html40" xmlns:q="http://schemas.xmlsoap.org/soap/envelope/" xmlns:rtc="http://microsoft.com/officenet/conferencing" xmlns:D="DAV:" xmlns:Repl="http://schemas.microsoft.com/repl/" xmlns:mt="http://schemas.microsoft.com/sharepoint/soap/meetings/" xmlns:x2="http://schemas.microsoft.com/office/excel/2003/xml" xmlns:ppda="http://www.passport.com/NameSpace.xsd" xmlns:ois="http://schemas.microsoft.com/sharepoint/soap/ois/" xmlns:dir="http://schemas.microsoft.com/sharepoint/soap/directory/" xmlns:ds="http://www.w3.org/2000/09/xmldsig#" xmlns:dsp="http://schemas.microsoft.com/sharepoint/dsp" xmlns:udc="http://schemas.microsoft.com/data/udc" xmlns:xsd="http://www.w3.org/2001/XMLSchema" xmlns:sub="http://schemas.microsoft.com/sharepoint/soap/2002/1/alerts/" xmlns:ec="http://www.w3.org/2001/04/xmlenc#" xmlns:sp="http://schemas.microsoft.com/sharepoint/" xmlns:sps="http://schemas.microsoft.com/sharepoint/soap/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:udcs="http://schemas.microsoft.com/data/udc/soap" xmlns:udcxf="http://schemas.microsoft.com/data/udc/xmlfile" xmlns:udcp2p="http://schemas.microsoft.com/data/udc/parttopart" xmlns:wf="http://schemas.microsoft.com/sharepoint/soap/workflow/" xmlns:dsss="http://schemas.microsoft.com/office/2006/digsig-setup" xmlns:dssi="http://schemas.microsoft.com/office/2006/digsig" xmlns:mdssi="http://schemas.openxmlformats.org/package/2006/digital-signature" xmlns:mver="http://schemas.openxmlformats.org/markup-compatibility/2006" xmlns:m="http://schemas.microsoft.com/office/2004/12/omml" xmlns:mrels="http://schemas.openxmlformats.org/package/2006/relationships" xmlns:spwp="http://microsoft.com/sharepoint/webpartpages" xmlns:ex12t="http://schemas.microsoft.com/exchange/services/2006/types" xmlns:ex12m="http://schemas.microsoft.com/exchange/services/2006/messages" xmlns:pptsl="http://schemas.microsoft.com/sharepoint/soap/SlideLibrary/" xmlns:spsl="http://microsoft.com/webservices/SharePointPortalServer/PublishedLinksService" xmlns:Z="urn:schemas-microsoft-com:" xmlns:st="" xmlns="http://www.w3.org/TR/REC-html40">
<head>
<meta http-equiv=Content-Type content="text/html; charset=us-ascii">
<meta name=Generator content="Microsoft Word 12 (filtered medium)">
<style>
<!--
/* Font Definitions */
@font-face
{font-family:Wingdings;
panose-1:5 0 0 0 0 0 0 0 0 0;}
@font-face
{font-family:Wingdings;
panose-1:5 0 0 0 0 0 0 0 0 0;}
@font-face
{font-family:Calibri;
panose-1:2 15 5 2 2 2 4 3 2 4;}
/* Style Definitions */
p.MsoNormal, li.MsoNormal, div.MsoNormal
{margin:0in;
margin-bottom:.0001pt;
font-size:11.0pt;
font-family:"Calibri","sans-serif";}
a:link, span.MsoHyperlink
{mso-style-priority:99;
color:blue;
text-decoration:underline;}
a:visited, span.MsoHyperlinkFollowed
{mso-style-priority:99;
color:purple;
text-decoration:underline;}
p.MsoListParagraph, li.MsoListParagraph, div.MsoListParagraph
{mso-style-priority:34;
margin-top:0in;
margin-right:0in;
margin-bottom:0in;
margin-left:.5in;
margin-bottom:.0001pt;
font-size:11.0pt;
font-family:"Calibri","sans-serif";}
span.EmailStyle17
{mso-style-type:personal-compose;
font-family:"Calibri","sans-serif";
color:windowtext;}
.MsoChpDefault
{mso-style-type:export-only;}
@page Section1
{size:8.5in 11.0in;
margin:1.0in 1.25in 1.0in 1.25in;}
div.Section1
{page:Section1;}
/* List Definitions */
@list l0
{mso-list-id:84496423;
mso-list-type:hybrid;
mso-list-template-ids:-35634446 67698705 67698713 67698715 67698703 67698713 67698715 67698703 67698713 67698715;}
@list l0:level1
{mso-level-text:"%1\)";
mso-level-tab-stop:none;
mso-level-number-position:left;
text-indent:-.25in;}
@list l1
{mso-list-id:223760741;
mso-list-type:hybrid;
mso-list-template-ids:1499860098 67698705 67698713 67698715 67698703 67698713 67698715 67698703 67698713 67698715;}
@list l1:level1
{mso-level-text:"%1\)";
mso-level-tab-stop:none;
mso-level-number-position:left;
text-indent:-.25in;}
@list l2
{mso-list-id:347561551;
mso-list-type:hybrid;
mso-list-template-ids:-1657757226 -13978720 67698691 67698693 67698689 67698691 67698693 67698689 67698691 67698693;}
@list l2:level1
{mso-level-start-at:10;
mso-level-number-format:bullet;
mso-level-text:-;
mso-level-tab-stop:none;
mso-level-number-position:left;
text-indent:-.25in;
font-family:"Calibri","sans-serif";
mso-fareast-font-family:Calibri;
mso-bidi-font-family:Arial;}
@list l3
{mso-list-id:1066030166;
mso-list-type:hybrid;
mso-list-template-ids:646866642 67698705 67698713 67698715 67698703 67698713 67698715 67698703 67698713 67698715;}
@list l3:level1
{mso-level-text:"%1\)";
mso-level-tab-stop:none;
mso-level-number-position:left;
text-indent:-.25in;}
@list l4
{mso-list-id:1224675873;
mso-list-type:hybrid;
mso-list-template-ids:-1170172098 67698705 67698713 67698715 67698703 67698713 67698715 67698703 67698713 67698715;}
@list l4:level1
{mso-level-text:"%1\)";
mso-level-tab-stop:none;
mso-level-number-position:left;
text-indent:-.25in;}
ol
{margin-bottom:0in;}
ul
{margin-bottom:0in;}
-->
</style>
<!--[if gte mso 9]><xml>
<o:shapedefaults v:ext="edit" spidmax="1026" />
</xml><![endif]--><!--[if gte mso 9]><xml>
<o:shapelayout v:ext="edit">
<o:idmap v:ext="edit" data="1" />
</o:shapelayout></xml><![endif]-->
</head>
<body lang=EN-US link=blue vlink=purple>
<div class=Section1>
<p class=MsoNormal>Dear GROMACS users,<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>When trying to simulate a pair of interacting proteins in
water, I have encountered problems that ultimately resulted in the simulation
crashing. I then tried to simplify the system as far as possible while
retaining the problem; I now believe the problem (or at least a part of it) lies
in the energy minimization step (the first molecular dynamics one). Specifically,
the forces encountered during this step are very large, and some water molecules
(which are supposed to be rigid) become giant and misshapen.<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>In more details:<o:p></o:p></p>
<p class=MsoNormal>1) I use GROMACS version 4.0.7, single precision, on a server
with two Intel x86-64 processors and the redhat 5.4 linux OS.<o:p></o:p></p>
<p class=MsoNormal>2) I created a PDB file, called NaCl.pdb, with only two “atoms”,
actually Na+ and Cl- ions separated by their distance in the lattice of salt:<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>HET NA A
1 1<o:p></o:p></p>
<p class=MsoNormal>HET CL A
1 1<o:p></o:p></p>
<p class=MsoNormal>HETNAM NA SODIUM ION<o:p></o:p></p>
<p class=MsoNormal>HETNAM CL CHLORIDE ION <o:p></o:p></p>
<p class=MsoNormal>FORMUL 1 NA NA 1+<o:p></o:p></p>
<p class=MsoNormal>FORMUL 2 CL CL 1- <o:p></o:p></p>
<p class=MsoNormal>HETATM 1 NA NA
A 1 -1.41
0.0 0.0 1.00
0.0 NA<o:p></o:p></p>
<p class=MsoNormal>HETATM 2 CL CL
A 1 +1.41
0.0 0.0 1.00
0.0 CL <o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>3) I use the tip3p water model:<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>pdb2gmx -f NaCl.pdb -water tip3p<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>4) I create the box:<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>editconf -f conf.gro -bt dodecahedron -d 3.3 -o box.gro<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>5) I add water using spc216, creating the saltwater.gro file
(which seems O.K. by inspection):<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>genbox -cp box.gro -cs spc216.gro -p topol.top -o
saltwater.gro<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>6) I create the energy minimization parameter file em.mdp:<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>------em.mdp------<o:p></o:p></p>
<p class=MsoNormal>integrator = steep <o:p></o:p></p>
<p class=MsoNormal>nsteps
= 200<o:p></o:p></p>
<p class=MsoNormal>nstlist = 10<o:p></o:p></p>
<p class=MsoNormal>rlist
= 1.0<o:p></o:p></p>
<p class=MsoNormal>coulombtype = pme<o:p></o:p></p>
<p class=MsoNormal>rcoulomb = 1.0<o:p></o:p></p>
<p class=MsoNormal>vdwtype =
Cut-off<o:p></o:p></p>
<p class=MsoNormal>rvdw
= 1.0<o:p></o:p></p>
<p class=MsoNormal>nstenergy = 10<o:p></o:p></p>
<p class=MsoNormal>------------------<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>7) I prepare the em.tpr file for the energy minimization
run:<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>grompp -f em.mdp -p topol.top -c saltwater.gro -o em.tpr<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>8) I run the energy minimization step:<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>mdrun -v -deffnm em<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>9) Looking at the em.log file I see that this step converged
to machine precision but did not have maximal force < 10:<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>…<o:p></o:p></p>
<p class=MsoNormal>Enabling SPC water optimization for 7561 molecules.<o:p></o:p></p>
<p class=MsoNormal>…<o:p></o:p></p>
<p class=MsoNormal>Max number of connections per atom is 2<o:p></o:p></p>
<p class=MsoNormal>Total number of connections is 30244<o:p></o:p></p>
<p class=MsoNormal>Max number of graph edges per atom is 2<o:p></o:p></p>
<p class=MsoNormal>Total number of graph edges is 30244<o:p></o:p></p>
<p class=MsoNormal>Going to use C-settle (7561 waters)<o:p></o:p></p>
<p class=MsoNormal>wo = 0.333333, wh =0.333333, wohh = 3, rc = 0.075695, ra =
0.0390588<o:p></o:p></p>
<p class=MsoNormal>rb = 0.0195294, rc2 = 0.15139, rone = 1, dHH = 0.15139, dOH
= 0.09572<o:p></o:p></p>
<p class=MsoNormal>…<o:p></o:p></p>
<p class=MsoNormal>Stepsize too small, or no change in energy.<o:p></o:p></p>
<p class=MsoNormal>Converged to machine precision,<o:p></o:p></p>
<p class=MsoNormal>but not to the requested precision Fmax < 10<o:p></o:p></p>
<p class=MsoNormal>…<o:p></o:p></p>
<p class=MsoNormal>Steepest Descents converged to machine precision in 36
steps,<o:p></o:p></p>
<p class=MsoNormal>but did not reach the requested Fmax < 10.<o:p></o:p></p>
<p class=MsoNormal>Potential Energy = -3.4678925e+05<o:p></o:p></p>
<p class=MsoNormal>Maximum force = 6.4623531e+05
on atom 11052<o:p></o:p></p>
<p class=MsoNormal>Norm of force = 5.4643726e+03<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>10) Looking at the em.gro file I see one monstrous water
molecule (no. 3686); e.g., it has |HW2-OW| = 3.384876 nm, while the normal
distance is about 0.1 nm. Its HW2 atom (no. 11054) is close to another water
molecule (no. 5849), e.g., 0.047 nm from the latter’s HW2 atom (no.
17543):<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>…<o:p></o:p></p>
<p class=MsoNormal>3686SOL OW11052
4.348 3.778 -0.629<o:p></o:p></p>
<p class=MsoNormal>3686SOL HW111053
5.360 2.601 0.505<o:p></o:p></p>
<p class=MsoNormal>3686SOL HW211054
6.518 1.650 0.861 <o:p></o:p></p>
<p class=MsoNormal>…<o:p></o:p></p>
<p class=MsoNormal>5849SOL OW17541
6.525 1.698 0.900<o:p></o:p></p>
<p class=MsoNormal>5849SOL HW117542
6.606 1.649 0.918<o:p></o:p></p>
<p class=MsoNormal>5849SOL HW217543
6.481 1.648 0.832<o:p></o:p></p>
<p class=MsoNormal>…<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>11) During the simulation, several files called stepnnl.pdb
were produced for problematic steps, where nn=11,15,19 and l=b,c. For example, the
file step19c.pdb indeed shows a problematic water molecule no. 3686, while
step19b.pdb does not. Likewise, the earlier step11c.pdb shows a problematic
water molecule no. 3266 while step11b.pdb seems proper. The stdout/stderr of mdrun
contains warnings like the following:<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>…<o:p></o:p></p>
<p class=MsoNormal>t = 0.019 ps: Water molecule starting at atom 11052 can not
be settled.<o:p></o:p></p>
<p class=MsoNormal>Check for bad contacts and/or reduce the timestep.<o:p></o:p></p>
<p class=MsoNormal>…<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>12) Reducing the neighbor list update time, i.e., setting nstlist
= 1, does not produce any change.<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>13) Trying to use the conjugate gradient integrator instead
of steepest descent, i.e., setting integrator = cg, is even worse - the running
crashes:<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>…<o:p></o:p></p>
<p class=MsoNormal>Step 16, Epot=-1.258771e+35,
Fnorm= nan, Fmax=
inf (atom 14493)<o:p></o:p></p>
<p class=MsoNormal>Segmentation fault<o:p></o:p></p>
<p class=MsoNormal>Exit 139<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>So, am I doing something wrong? How can I avoid these
problems?<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
<p class=MsoNormal>Thanks,<o:p></o:p></p>
<p class=MsoNormal>Ehud Schreiber.<o:p></o:p></p>
<p class=MsoNormal><o:p> </o:p></p>
</div>
</body>
</html>