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Conformational Sampling |
Examples and Guides |
1 |
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A simple conformational search. |
/page/examples/example_1.html |
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The default application of CREST is the iMTD-GC workflow. In the following, a standard production run with this workflow is shown for the alanineglycine molecule. {: .text-justify }
{% include image.html file="example_1_1.png" alt="Ala-Gly input structure" caption="Input structure of the alanineglycine molecule." max-width=300%}
Let’s assume that we are interested in the conformations of Ala-Gly at the GFN2-xTB level with GBSA implicit solvation for water, and that we are using 4 CPU threads.
Assuming further that our initial input structure (atomic coordinates, here in Ångström) are given in a file struc.xyz, then the conformational search can be initiated from the command line via:
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command
{{ site.data.icons.codefile }} struc.xyz
{{ site.data.icons.checkfile }} output
C 2.081440 0.615100 -0.508430 C 2.742230 1.824030 -1.200820 N 4.117790 1.799870 -1.190410 C 4.943570 2.827040 -1.822060 C 6.440080 2.569360 -1.637600 O 7.351600 3.252270 -2.069090 N 0.610100 0.695090 -0.538780 O 2.095560 2.724940 -1.739670 O 6.705220 1.463410 -0.897460 H 0.303080 1.426060 0.103770 H 0.338420 1.050680 -1.460480 C 2.488753 -0.593400 -1.198448 H 2.416500 0.557400 0.532050 H 4.614100 1.081980 -0.670550 H 4.699850 3.794460 -1.373720 H 4.722890 2.844690 -2.894180 H 7.687400 1.448620 -0.860340 H 2.029201 -1.457008 -0.719999 H 2.170233 -0.542411 -2.238576 H 3.572730 -0.688405 -1.154998 {% endcapture %} {% include codecell.html content=struc_xyz %}
Cite work conducted with this code as
P. Pracht, F. Bohle, S. Grimme, PCCP, 2020, 22, 7169-7192.
and S. Grimme, JCTC, 2019, 15, 2847-2862.
with help from: C.Bannwarth, F.Bohle, S.Ehlert, S.Grimme, P.Pracht, S. Spicher
This program is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.
Command line input:
crest struc.xyz --gfn2 --gbsa h2o -T 4
-gfn2 : Use of GFN2-xTB requested. --gbsa h2o : implicit solvation -T 4 (CPUs/Threads selected)
Geometry successfully optimized.
Calculating WBOs... done. Calculating NCI flexibility... done. covalent flexibility measure : 0.450 non-covalent flexibility measure : 0.823 flexibility measure : 0.501 t(MTD) / ps : 5.0 Σ(t(MTD)) / ps : 70.0 (14 MTDs)
Estimated runtime for one MTD (5.0 ps) on a single thread: 19 sec Estimated runtime for a batch of 14 MTDs on 4 threads: 1 min 15 sec
list of Vbias parameters applied: $metadyn 0.00300 1.300 $metadyn 0.00150 1.300 $metadyn 0.00075 1.300 $metadyn 0.00300 0.780 $metadyn 0.00150 0.780 $metadyn 0.00075 0.780 $metadyn 0.00300 0.468 $metadyn 0.00150 0.468 $metadyn 0.00075 0.468 $metadyn 0.00300 0.281 $metadyn 0.00150 0.281 $metadyn 0.00075 0.281 $metadyn 0.00100 0.100 $metadyn 0.00500 0.800
** N E W I T E R A T I O N C Y C L E **
========================================
| Meta-MD (MTD) Sampling |
========================================
<.......>
- crude pre-optimization
Optimizing all 686 structures from file "crest_rotamers_0.xyz" ... <.......> done. running RMSDs... done. E lowest : -33.87998 654 structures remain within 12.00 kcal/mol window
- optimization with tight thresholds
Optimizing all 655 structures from file "crest_rotamers_1.xyz" ... <.......> done. running RMSDs... done. E lowest : -33.88023 119 structures remain within 6.00 kcal/mol window
<.......> <.......>
Collecting ensmbles. running RMSDs... done. E lowest : -33.88023 146 structures remain within 6.00 kcal/mol window
<.......> Appending file crest_rotamers_1.xyz with new structures
Optimizing all 338 structures from file "crest_rotamers_1.xyz" ... <.......> done. running RMSDs... done. E lowest : -33.88023 159 structures remain within 6.00 kcal/mol window
========================================
| Structure Crossing (GC) |
========================================
=============================
============================= input file name : crest_rotamers_3.xyz number of atoms : 20 number of points on xyz files : 159 conformer energy window /kcal : 6.00 CN per atom difference cut-off : 0.3000 RMSD threshold : 0.2500 max. # of generated structures : 250 reading xyz file ...
generating pairs ... 12719 66.0 % done generated pairs : 10762 number of clash discarded : 1799 average rmsd w.r.t input : 2.82636 sd of ensemble : 0.63885 number of new structures : 98 removed identical structures : 402 <.......> <.......>
Optimizing all 170 structures from file "crest_rotamers_4.xyz" ... <.......> done. running RMSDs... done. E lowest : -33.88023 147 structures remain within 6.00 kcal/mol window
input file name : crest_rotamers_5.xyz output file name : crest_rotamers_6.xyz number of atoms : 20 number of points on xyz files : 170 RMSD threshold : 0.1250 Bconst threshold : 0.0100 population threshold : 0.0500 conformer energy window /kcal : 6.0000
number of reliable points : 170 reference state Etot : -33.8802280500000 number of doubles removed by rot/RMSD : 23 total number unique points considered further : 147 Erel/kcal Etot weight/tot conformer set degen origin 1 0.000 -33.88023 0.04207 0.25214 1 6 gc 2 0.000 -33.88023 0.04204 mtd1 3 0.001 -33.88023 0.04203 mtd9 4 0.001 -33.88023 0.04200 gc 5 0.001 -33.88023 0.04200 mtd3 6 0.001 -33.88023 0.04200 mtd9 7 0.050 -33.88015 0.03865 0.19312 2 5 mtd3 8 0.050 -33.88015 0.03864 mtd14 9 0.051 -33.88015 0.03862 mtd10 10 0.051 -33.88015 0.03861 md5 11 0.051 -33.88015 0.03860 mtd9 12 0.476 -33.87947 0.01884 0.09414 3 5 md6 13 0.476 -33.87947 0.01884 mtd12 14 ... 15 ...
<.......>
T /K : 298.15 E lowest : -33.88023 ensemble average energy (kcal) : 0.550 ensemble entropy (J/mol K, cal/mol K) : 34.054 8.139 ensemble free energy (kcal/mol) : -2.427 population of lowest in % : 25.214 number of unique conformers for further calc 61 list of relative energies saved as "crest.energies"
<.......>
CREST terminated normally. {% endcapture %} {% include codecell.html content=output_file %}
{% include tip.html content="It's usually wise to pre-optimze your input structure with xtb at the same level on which the conformational search shall be conducted. Since the input structure is taken as a reference for several topology checks within the sorting routine, such as unchanging coordination numbers of the atoms, providing a structure on the same level of theory is recommended." %}
The program call first creates a coord file from the given input structure.
Then, settings such as the length of the MTD simulation are automatically determined from a molecular flexibility measure.
With these settings, the workflow as presented here is conducted.
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The production run in this example yields 147 structures of Ala-Gly, distributed over 61 different conformers within 6 kcal/mol above the lowest conformer that was found at the search level. The three lowest conformers at the search level are shown below. {: .text-justify }
{% include image.html file="example_1_2.png" alt="Ala-Gly conformers" caption="Three lowest conformers of alanineglycine generated by CREST at the GFN2-xTB/GBSA(H2O) level." %}
Each of the 61 conformers may shows several rotamers, which by definition are degenerate forms of the respective confromer.
The final ensemble of all the found conformers is written to an ensemble file in the Xmol format called crest_conformers.xyz. The corresponding CRE, i.e., the ensemble containing conformers and rotamers is written to the file crest_rotamers.xyz.
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