Dear all, <div><br></div><div><meta http-equiv="content-type" content="text/html; charset=utf-8"><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; ">We have tested more strange behavior of constraints from pull code for calculation of free energy differences small molecule on DOPC membrane and octanol slab. </span></div>
<div><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; ">As I have reported previously, while the errors in free energy differences on DOPC were rather small, the errors on octanol were strangely high.</span></div>
<div><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; "><br></span></div><div><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; ">We have prepared smaller slabs (as Mark suggested) of octanol with comparable size of box and we have also tried to analyze the position of centres either via pullx.xvg provided by pull code, but also by g_dist utility and to our surprise, size matters. A lot. </span></div>
<div><font class="Apple-style-span" face="arial, sans-serif"><span class="Apple-style-span" style="border-collapse: collapse;">(Same groups were used in mdp for pull and for g_dist analysis, only distances in z-axis is shown)<br>
</span></font><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; "><div><br></div><div>DOPC, 128 molecules, box size 6.2 6.4 8.3 , position of small molecule on the edge of membrane</div>
</span><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; "><meta http-equiv="content-type" content="text/html; charset=utf-8">Time(ps) </span><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; ">pullf.xvg dist.xvg</span></div>
<div><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; "></span><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; "> 0.00 -0.12416 -0.12436</span><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; "><div>
<div> 1.00 -0.12416 -0.12433</div><div> 2.00 -0.12416 -0.12428</div><div> 3.00 -0.12416 -0.12430</div><div> 4.00 -0.12416 -0.12430</div><div> 5.00 -0.12416 -0.12432</div>
<div> 6.00 -0.12416 -0.12434</div></div></span><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; "> 7.00 -0.12416 -0.12449</span></div><div><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; "></span><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; ">As can be seen, the variation of distances reported by these two programs is not perfect, but it is rather ok with precision of about 0.001 nm. </span><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; "><div>
<br></div></span><div style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; "><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; ">Octanol, 957 molecules, box size 5.7 5.9 13.7, position is similar on the edge of slab, errors in free energy profiles are mainly here.</span></div>
<span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; "><meta http-equiv="content-type" content="text/html; charset=utf-8">Time(ps) </span><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; ">pullf.xvg dist.xvg</span></div>
<div><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; "></span><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; "> 0.00 -2.81855 -3.41133</span><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; "><div>
<span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; "><div> 1.00 -2.81076 -3.44213</div><div> 2.00 -2.82005 -3.27949</div><div> 3.00 -2.81856 -3.35097</div>
<div> 4.00 -2.82016 -3.50378</div><div> 5.00 -2.81849 -3.63261</div><div> 6.00 -2.81855 -3.60058</div><div> 7.00 -2.81870 -3.80251</div><div> 8.00 -2.81859 -3.32790</div>
<div> 9.00 -2.81849 -3.24329</div><div> 10.00 -2.81855 -3.28394</div></span></div></span><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; "> 21.00 -2.81855 -4.02524</span></div>
<div><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; "></span><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; "><div>
<span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; "><div>Here, the distances reported by pull code and by g_dist are completely different with differences in about 1 nm! Visual inspection in VMD says that small molecule is highly mobile a actual distances are reported rightly by g_dist program. </div>
<div><meta http-equiv="content-type" content="text/html; charset=utf-8"><span class="Apple-style-span" style="font-family: arial; font-size: small; border-collapse: separate; "><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; ">Strangely enough, when we put distance measured by g_dist as a start into the pull code without guessing the distances, but this also did not worked, since the molecule tried to be at some completely different position and the simulation crashed as the molecule speeded up. </span><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; "><div>
<span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; "></span></div></span></span></div></span></div></span><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; "><div>
<span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; "><br></span></div></span><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; font-size: 13px; ">Octanol, 475 molecules, box size 5.5 5.5 9.5, position also on the edge of the slab</span></div>
<div><span class="Apple-style-span" style="border-collapse: collapse; font-family: arial, sans-serif; ">Time(ps) pullf.xvg dist.xvg</span><font class="Apple-style-span" face="arial, sans-serif"><span class="Apple-style-span" style="border-collapse: collapse;"><div>
0.00 -0.49996 -0.49989</div><div> 1.00 -0.49996 -0.49988</div><div> 2.00 -0.49996 -0.49981</div><div> 3.00 -0.49996 -0.49981</div><div> 4.00 -0.49996 -0.50001</div><div>
5.00 -0.49996 -0.49987</div><div> 6.00 -0.49996 -0.49986</div><div> 7.00 -0.49996 -0.49994</div><div> 8.00 -0.49997 -0.49988</div><div> 9.00 -0.49996 -0.49980</div><div>
10.00 -0.49996 -0.49988</div></span></font><div style="font-size: 13px; border-collapse: collapse; font-family: arial, sans-serif; ">Smaller box cured miraculously the problem, since here the difference is similarly small as in DOPC case. </div>
<div style="font-size: 13px; border-collapse: collapse; font-family: arial, sans-serif; "><br></div><div style="font-size: 13px; border-collapse: collapse; font-family: arial, sans-serif; ">However just to remind another ache we had with octanol slab, in case of octanol, the size of box in xy plane had to be held constant as the box narrowed thorough the whole simulation when in anisotropic NPT ensemble. </div>
<div style="font-size: 13px; border-collapse: collapse; font-family: arial, sans-serif; "><br></div><div style="font-size: 13px; border-collapse: collapse; font-family: arial, sans-serif; ">Why g_dist and pullx show so different results in large box, I still do not understand. Any suggestions? </div>
<div style="font-size: 13px; border-collapse: collapse; font-family: arial, sans-serif; ">And possibly any suggestions whether our box narrowing in case of octanol is common or do we have another devil hidden there? </div>
<div><br></div><div>Best wishes</div>-- <br>Zdraví skoro zdravý<br>Karel "Krápník" Berka<br><br>****************************************************************<br>RNDr. Karel Berka, Ph.D.<br>Palacký University in Olomouc<br>
Faculty of Science<br>Department of Physical Chemistry<br>tř. 17. listopadu 1192/12<br>771 46 Olomouc<br>tel: +420-585634769 <br>fax: +420-585634769<br>e-mail: <a href="mailto:karel.berka@upol.cz">karel.berka@upol.cz</a><br>
<br>****************************************************************<br>
</div>