Metadynamics-based Conformational Sampling
A simple conformational search based on metadynamics simulations.
Standard Conformational Search (iMTD-GC)
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.
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:
crest input.tomlcrest struc.xyz --gfn2 --gbsa h2o -T 4input.toml file (CREST >= 3.0), while the second version is the standard CMD version. Here, --gfn2 specifies the usage of the SQM level GFN2-xTB, --gbsa h2o implements the GBSA implicit solvation for water, and -T 4 requests the usage of 4 CPU threads. You can save the terminal output of this command by adding > crest.out at the end of the line. The output will look something like the one in the output tab above.
# This is a CREST input file
input = "struc.xyz"
runtype = "imtd-gc"
threads = 4
[calculation]
[[calculation.level]]
method = "gfn2"
alpb = "h2o"
20
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
╔════════════════════════════════════════════╗
║ ___ ___ ___ ___ _____ ║
║ / __| _ \ __/ __|_ _| ║
║ | (__| / _|\__ \ | | ║
║ \___|_|_\___|___/ |_| ║
║ ║
║ Conformer-Rotamer Ensemble Sampling Tool ║
║ based on the xTB methods ║
║ ║
╚════════════════════════════════════════════╝
Version 3.0.2, Thu, 17 April 13:37:10, 04/17/2025
commit (f7fb5bf) compiled by 'usr@stellaris'
Cite work conducted with this code as
• P.Pracht, F.Bohle, S.Grimme, PCCP, 2020, 22, 7169-7192.
• S.Grimme, JCTC, 2019, 15, 2847-2862.
• P.Pracht, S.Grimme, C.Bannwarth, F.Bohle, S.Ehlert,
G.Feldmann, J.Gorges, M.Müller, T.Neudecker, C.Plett,
S.Spicher, P.Steinbach, P.Wesołowski, F.Zeller,
J. Chem. Phys., 2024, 160, 114110.
for works involving QCG cite
• S.Spicher, C.Plett, P.Pracht, A.Hansen, S.Grimme,
JCTC, 2022, 18 (5), 3174-3189.
• C.Plett, S. Grimme,
Angew. Chem. Int. Ed. 2023, 62, e202214477.
for works involving MECP screening cite
• P.Pracht, C.Bannwarth, JCTC, 2022, 18 (10), 6370-6385.
Original code
P.Pracht, S.Grimme, Universität Bonn, MCTC
with help from (alphabetical order):
C.Bannwarth, F.Bohle, S.Ehlert, G.Feldmann, J.Gorges,
S.Grimme, C.Plett, P.Pracht, S.Spicher, P.Steinbach,
P.Wesolowski, F.Zeller
Online documentation is available at
https://crest-lab.github.io/crest-docs/
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. See the
GNU Lesser General Public License (LGPL) for more details.
Command line input:
$ crest input.toml
reading input.toml
********************************************************************************
* INPUT FILE input.toml content (without comments):
********************************************************************************
* input = "struc.xyz"
* runtype = "imtd-gc"
* threads = 4
* [calculation]
* [[calculation.level]]
* method = "gfn2"
* alpb = "h2o"
********************************************************************************
┍━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━┑
│ CREST iMTD-GC SAMPLING │
┕━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━┙
Input structure:
20
C -2.2423217693 -0.5287748502 0.3281832641
C -1.1339831252 0.5138443877 0.0790053036
N 0.1426014202 0.0020152962 0.1139376188
C 1.3372946099 0.8069729173 -0.1324846822
C 2.6267170075 -0.0061636567 -0.0053412725
O 3.7614500516 0.4039758427 -0.1714283230
N -3.5874195683 0.0724101912 0.2901126031
O -1.3698068126 1.7010887734 -0.1555542767
O 2.4112957426 -1.2994221527 0.3443843098
H -3.7216414427 0.6412963530 1.1266542620
H -3.5997567190 0.7551890933 -0.4737237184
C -2.1646252935 -1.5431812466 -0.7049884984
H -2.0890731880 -1.0044531303 1.3020611672
H 0.3005013399 -0.9639003709 0.3860012642
H 1.3661729845 1.6204173883 0.5981203975
H 1.2821178923 1.2158719637 -1.1464913779
H 3.3195884712 -1.6714184648 0.3982104550
H -2.9425094897 -2.2876579894 -0.5419829138
H -2.3046618238 -1.0794238939 -1.6803038386
H -1.1883522567 -2.0243141103 -0.6686276085
------------------------------------------------
Generating MTD length from a flexibility measure
------------------------------------------------
Calculating GFN0-xTB WBOs ... done.
Calculating NCI flexibility ... done.
covalent flexibility measure : 0.460
non-covalent flexibility measure : 0.822
flexibility measure : 0.508
t(MTD) / ps : 6.0
Σ(t(MTD)) / ps : 84.0 (14 MTDs)
-----------------------------------
Starting trial MTD to test settings
-----------------------------------
Trial MTD 1 runtime (1.0 ps) ... 0 min, 1.142 sec
Estimated runtime for one MTD (6.0 ps) on a single thread: 7 sec
Estimated runtime for a batch of 14 MTDs on 4 threads: 27 sec
******************************************************************************************
** N E W I T E R A T I O N C Y C L E **
******************************************************************************************
------------------------------
Meta-Dynamics Iteration 1
------------------------------
list of applied metadynamics Vbias parameters:
$metadyn 0.06000 1.300
$metadyn 0.03000 1.300
$metadyn 0.01500 1.300
$metadyn 0.06000 0.780
$metadyn 0.03000 0.780
$metadyn 0.01500 0.780
$metadyn 0.06000 0.468
$metadyn 0.03000 0.468
$metadyn 0.01500 0.468
$metadyn 0.06000 0.281
$metadyn 0.03000 0.281
$metadyn 0.01500 0.281
$metadyn 0.02000 0.100
$metadyn 0.10000 0.800
::::::::::::: starting MTD 12 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0150 Eh |
| Vbias exponent (α) : 0.2808 bohr⁻² |
::::::::::::: starting MTD 1 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0600 Eh |
| Vbias exponent (α) : 1.3000 bohr⁻² |
::::::::::::: starting MTD 5 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0300 Eh |
| Vbias exponent (α) : 0.7800 bohr⁻² |
::::::::::::: starting MTD 9 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0150 Eh |
| Vbias exponent (α) : 0.4680 bohr⁻² |
*MTD 12 completed successfully ... 0 min, 7.396 sec
::::::::::::: starting MTD 13 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0200 Eh |
| Vbias exponent (α) : 0.1000 bohr⁻² |
*MTD 1 completed successfully ... 0 min, 7.446 sec
::::::::::::: starting MTD 2 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0300 Eh |
| Vbias exponent (α) : 1.3000 bohr⁻² |
*MTD 5 completed successfully ... 0 min, 7.449 sec
::::::::::::: starting MTD 6 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0150 Eh |
| Vbias exponent (α) : 0.7800 bohr⁻² |
*MTD 9 completed successfully ... 0 min, 7.486 sec
::::::::::::: starting MTD 10 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0600 Eh |
| Vbias exponent (α) : 0.2808 bohr⁻² |
*MTD 13 completed successfully ... 0 min, 7.437 sec
::::::::::::: starting MTD 14 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.1000 Eh |
| Vbias exponent (α) : 0.8000 bohr⁻² |
*MTD 2 completed successfully ... 0 min, 7.455 sec
::::::::::::: starting MTD 3 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0150 Eh |
| Vbias exponent (α) : 1.3000 bohr⁻² |
*MTD 6 completed successfully ... 0 min, 7.495 sec
::::::::::::: starting MTD 7 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0600 Eh |
| Vbias exponent (α) : 0.4680 bohr⁻² |
*MTD 10 completed successfully ... 0 min, 7.492 sec
::::::::::::: starting MTD 11 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0300 Eh |
| Vbias exponent (α) : 0.2808 bohr⁻² |
*MTD 14 completed successfully ... 0 min, 7.504 sec
*MTD 11 completed successfully ... 0 min, 7.420 sec
*MTD 7 completed successfully ... 0 min, 7.481 sec
::::::::::::: starting MTD 8 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0300 Eh |
| Vbias exponent (α) : 0.4680 bohr⁻² |
*MTD 3 completed successfully ... 0 min, 7.588 sec
::::::::::::: starting MTD 4 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0600 Eh |
| Vbias exponent (α) : 0.7800 bohr⁻² |
*MTD 4 completed successfully ... 0 min, 8.762 sec
*MTD 8 completed successfully ... 0 min, 8.884 sec
======================================
| Multilevel Ensemble Optimization |
======================================
Optimizing all 826 structures from file "crest_dynamics.trj" ...
----------------------
crude pre-optimization
----------------------
Optimization engine: ANCOPT
Hessian update type: BFGS
E/G convergence criteria: 0.500E-03 Eh, 0.100E-01 Eh/a0
maximum optimization steps: 200
|>0.1% |>10.0% |>20.1% |>30.0% |>40.1% |>50.0% |>60.0% |>70.1% |>80.0% |>90.1% |>100.0%
done.
> 826 of 826 structures successfully optimized (100.0% success)
> Total runtime for 826 optimizations:
* wall-time: 0 d, 0 h, 0 min, 14.061 sec
* cpu-time: 0 d, 0 h, 0 min, 56.176 sec
* ratio c/w: 3.995 speedup
> Corresponding to approximately 0.017 sec per processed structure
CREGEN> running RMSDs ... done.
CREGEN> E lowest : -33.88416
749 structures remain within 12.00 kcal/mol window
----------------------------------
optimization with tight thresholds
----------------------------------
Optimization engine: ANCOPT
Hessian update type: BFGS
E/G convergence criteria: 0.100E-05 Eh, 0.800E-03 Eh/a0
maximum optimization steps: 200
|>0.1% |>10.0% |>20.0% |>30.0% |>40.1% |>50.1% |>60.1% |>70.1% |>80.1% |>90.1% |>100.0%
done.
> 749 of 749 structures successfully optimized (100.0% success)
> Total runtime for 749 optimizations:
* wall-time: 0 d, 0 h, 0 min, 47.941 sec
* cpu-time: 0 d, 0 h, 3 min, 11.161 sec
* ratio c/w: 3.987 speedup
> Corresponding to approximately 0.064 sec per processed structure
CREGEN> running RMSDs ... done.
CREGEN> E lowest : -33.88486
119 structures remain within 6.00 kcal/mol window
------------------------------
Meta-Dynamics Iteration 2
------------------------------
list of applied metadynamics Vbias parameters:
$metadyn 0.06000 1.300
$metadyn 0.03000 1.300
$metadyn 0.01500 1.300
$metadyn 0.06000 0.780
$metadyn 0.03000 0.780
$metadyn 0.01500 0.780
$metadyn 0.06000 0.468
$metadyn 0.03000 0.468
$metadyn 0.01500 0.468
$metadyn 0.06000 0.281
$metadyn 0.03000 0.281
$metadyn 0.01500 0.281
$metadyn 0.02000 0.100
$metadyn 0.10000 0.800
::::::::::::: starting MTD 1 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0600 Eh |
| Vbias exponent (α) : 1.3000 bohr⁻² |
::::::::::::: starting MTD 9 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0150 Eh |
| Vbias exponent (α) : 0.4680 bohr⁻² |
::::::::::::: starting MTD 5 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0300 Eh |
| Vbias exponent (α) : 0.7800 bohr⁻² |
::::::::::::: starting MTD 12 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0150 Eh |
| Vbias exponent (α) : 0.2808 bohr⁻² |
*MTD 9 completed successfully ... 0 min, 7.768 sec
::::::::::::: starting MTD 10 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0600 Eh |
| Vbias exponent (α) : 0.2808 bohr⁻² |
*MTD 5 completed successfully ... 0 min, 7.778 sec
::::::::::::: starting MTD 6 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0150 Eh |
| Vbias exponent (α) : 0.7800 bohr⁻² |
*MTD 12 completed successfully ... 0 min, 7.783 sec
::::::::::::: starting MTD 13 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0200 Eh |
| Vbias exponent (α) : 0.1000 bohr⁻² |
*MTD 1 completed successfully ... 0 min, 7.867 sec
::::::::::::: starting MTD 2 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0300 Eh |
| Vbias exponent (α) : 1.3000 bohr⁻² |
*MTD 6 completed successfully ... 0 min, 7.988 sec
::::::::::::: starting MTD 7 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0600 Eh |
| Vbias exponent (α) : 0.4680 bohr⁻² |
*MTD 10 completed successfully ... 0 min, 8.029 sec
::::::::::::: starting MTD 11 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0300 Eh |
| Vbias exponent (α) : 0.2808 bohr⁻² |
*MTD 13 completed successfully ... 0 min, 8.034 sec
::::::::::::: starting MTD 14 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.1000 Eh |
| Vbias exponent (α) : 0.8000 bohr⁻² |
*MTD 2 completed successfully ... 0 min, 8.054 sec
::::::::::::: starting MTD 3 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0150 Eh |
| Vbias exponent (α) : 1.3000 bohr⁻² |
*MTD 7 completed successfully ... 0 min, 7.702 sec
::::::::::::: starting MTD 8 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0300 Eh |
| Vbias exponent (α) : 0.4680 bohr⁻² |
*MTD 14 completed successfully ... 0 min, 7.656 sec
*MTD 11 completed successfully ... 0 min, 7.781 sec
*MTD 3 completed successfully ... 0 min, 7.743 sec
::::::::::::: starting MTD 4 :::::::::::::
| MD simulation time : 6.0 ps |
| target T : 300.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
| dump interval(Vbias) : 1.00 ps |
| Vbias prefactor (k) : 0.0600 Eh |
| Vbias exponent (α) : 0.7800 bohr⁻² |
*MTD 8 completed successfully ... 0 min, 9.067 sec
*MTD 4 completed successfully ... 0 min, 9.194 sec
======================================
| Multilevel Ensemble Optimization |
======================================
Optimizing all 826 structures from file "crest_dynamics.trj" ...
----------------------
crude pre-optimization
----------------------
Optimization engine: ANCOPT
Hessian update type: BFGS
E/G convergence criteria: 0.500E-03 Eh, 0.100E-01 Eh/a0
maximum optimization steps: 200
|>0.1% |>10.0% |>20.1% |>30.0% |>40.1% |>50.0% |>60.0% |>70.1% |>80.0% |>90.1% |>100.0%
done.
> 826 of 826 structures successfully optimized (100.0% success)
> Total runtime for 826 optimizations:
* wall-time: 0 d, 0 h, 0 min, 16.578 sec
* cpu-time: 0 d, 0 h, 1 min, 5.977 sec
* ratio c/w: 3.980 speedup
> Corresponding to approximately 0.020 sec per processed structure
CREGEN> running RMSDs ... done.
CREGEN> E lowest : -33.88433
730 structures remain within 12.00 kcal/mol window
----------------------------------
optimization with tight thresholds
----------------------------------
Optimization engine: ANCOPT
Hessian update type: BFGS
E/G convergence criteria: 0.100E-05 Eh, 0.800E-03 Eh/a0
maximum optimization steps: 200
|>0.1% |>10.0% |>20.0% |>30.0% |>40.0% |>50.0% |>60.0% |>70.1% |>80.0% |>90.1% |>100.0%
done.
> 730 of 730 structures successfully optimized (100.0% success)
> Total runtime for 730 optimizations:
* wall-time: 0 d, 0 h, 1 min, 7.022 sec
* cpu-time: 0 d, 0 h, 4 min, 27.152 sec
* ratio c/w: 3.986 speedup
> Corresponding to approximately 0.092 sec per processed structure
CREGEN> running RMSDs ... done.
CREGEN> E lowest : -33.88486
106 structures remain within 6.00 kcal/mol window
========================================
MTD Simulations done
========================================
Collecting ensmbles.
CREGEN> running RMSDs ... done.
CREGEN> E lowest : -33.88486
148 structures remain within 6.00 kcal/mol window
===============================================
Additional regular MDs on lowest 4 conformer(s)
===============================================
:::::::::::::: starting MD 8 ::::::::::::::
| MD simulation time : 3.0 ps |
| target T : 500.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
:::::::::::::: starting MD 1 ::::::::::::::
| MD simulation time : 3.0 ps |
| target T : 400.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
:::::::::::::: starting MD 2 ::::::::::::::
| MD simulation time : 3.0 ps |
| target T : 400.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
:::::::::::::: starting MD 3 ::::::::::::::
| MD simulation time : 3.0 ps |
| target T : 400.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
*MD 2 completed successfully ... 0 min, 3.834 sec
:::::::::::::: starting MD 4 ::::::::::::::
| MD simulation time : 3.0 ps |
| target T : 400.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
*MD 3 completed successfully ... 0 min, 3.839 sec
:::::::::::::: starting MD 5 ::::::::::::::
| MD simulation time : 3.0 ps |
| target T : 500.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
*MD 8 completed successfully ... 0 min, 3.876 sec
:::::::::::::: starting MD 7 ::::::::::::::
| MD simulation time : 3.0 ps |
| target T : 500.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
*MD 1 completed successfully ... 0 min, 3.882 sec
:::::::::::::: starting MD 6 ::::::::::::::
| MD simulation time : 3.0 ps |
| target T : 500.0 K |
| timestep dt : 5.0 fs |
| dump interval(trj) : 100.0 fs |
| SHAKE algorithm : true (all bonds) |
*MD 4 completed successfully ... 0 min, 3.857 sec
*MD 5 completed successfully ... 0 min, 3.892 sec
*MD 6 completed successfully ... 0 min, 3.883 sec
*MD 7 completed successfully ... 0 min, 3.892 sec
Appending file crest_rotamers_1.xyz with new structures
Optimizing all 380 structures from file "crest_rotamers_1.xyz" ...
----------------------------------
optimization with tight thresholds
----------------------------------
Optimization engine: ANCOPT
Hessian update type: BFGS
E/G convergence criteria: 0.100E-05 Eh, 0.800E-03 Eh/a0
maximum optimization steps: 200
|>0.3% |>10.0% |>20.0% |>30.0% |>40.0% |>50.0% |>60.0% |>70.3% |>80.0% |>90.3% |>100.0%
done.
> 380 of 380 structures successfully optimized (100.0% success)
> Total runtime for 380 optimizations:
* wall-time: 0 d, 0 h, 0 min, 15.766 sec
* cpu-time: 0 d, 0 h, 1 min, 2.843 sec
* ratio c/w: 3.986 speedup
> Corresponding to approximately 0.041 sec per processed structure
CREGEN> running RMSDs ... done.
CREGEN> E lowest : -33.88488
150 structures remain within 6.00 kcal/mol window
========================================
| Structure Crossing (GC) |
========================================
=============================
# threads = 4
=============================
input file name : crest_rotamers_2.xyz
number of atoms : 20
number of points on xyz files : 150
conformer energy window /kcal : 6.00
CN per atom difference cut-off : 0.3000
RMSD threshold (Ang, Bohr) : 0.2500 0.4724
max. # of generated structures : 300
# in E window 150
11.7 % done
38.0 % done
61.9 % done
85.4 % done
finished.
average rmsd w.r.t input : 2.78725
number of clash discarded : 192
removed identical structures : 227
300 structures written to confcross.xyz
======================================
| Multilevel Ensemble Optimization |
======================================
Optimizing all 300 structures from file "confcross.xyz" ...
----------------------
crude pre-optimization
----------------------
Optimization engine: ANCOPT
Hessian update type: BFGS
E/G convergence criteria: 0.500E-03 Eh, 0.100E-01 Eh/a0
maximum optimization steps: 200
|>0.3% |>10.0% |>20.0% |>30.0% |>40.0% |>50.0% |>60.0% |>70.3% |>80.0% |>90.3% |>100.0%
done.
> 300 of 300 structures successfully optimized (100.0% success)
> Total runtime for 300 optimizations:
* wall-time: 0 d, 0 h, 0 min, 3.825 sec
* cpu-time: 0 d, 0 h, 0 min, 14.952 sec
* ratio c/w: 3.909 speedup
> Corresponding to approximately 0.013 sec per processed structure
CREGEN> running RMSDs ... done.
CREGEN> E lowest : -33.88483
214 structures remain within 12.00 kcal/mol window
----------------------------------
optimization with tight thresholds
----------------------------------
Optimization engine: ANCOPT
Hessian update type: BFGS
E/G convergence criteria: 0.100E-05 Eh, 0.800E-03 Eh/a0
maximum optimization steps: 200
|>0.5% |>10.3% |>20.1% |>30.4% |>40.2% |>50.0% |>60.3% |>70.1% |>80.4% |>90.2% |>100.0%
done.
> 214 of 214 structures successfully optimized (100.0% success)
> Total runtime for 214 optimizations:
* wall-time: 0 d, 0 h, 0 min, 12.535 sec
* cpu-time: 0 d, 0 h, 0 min, 49.451 sec
* ratio c/w: 3.945 speedup
> Corresponding to approximately 0.059 sec per processed structure
CREGEN> running RMSDs ... done.
CREGEN> E lowest : -33.88488
62 structures remain within 6.00 kcal/mol window
appending new structures to crest_rotamers_2.xyz
CREGEN> running RMSDs ... done.
CREGEN> E lowest : -33.88488
================================================
| Final Geometry Optimization |
================================================
Optimizing all 162 structures from file "crest_rotamers_3.xyz" ...
---------------------------------------
optimization with very tight thresholds
---------------------------------------
Optimization engine: ANCOPT
Hessian update type: BFGS
E/G convergence criteria: 0.100E-06 Eh, 0.200E-03 Eh/a0
maximum optimization steps: 200
|>0.6% |>10.5% |>20.4% |>30.2% |>40.1% |>50.0% |>60.5% |>70.4% |>80.2% |>90.1% |>100.0%
done.
> 162 of 162 structures successfully optimized (100.0% success)
> Total runtime for 162 optimizations:
* wall-time: 0 d, 0 h, 0 min, 7.110 sec
* cpu-time: 0 d, 0 h, 0 min, 27.747 sec
* ratio c/w: 3.903 speedup
> Corresponding to approximately 0.044 sec per processed structure
CREGEN> running RMSDs ... done.
CREGEN> E lowest : -33.88484
117 structures remain within 6.00 kcal/mol window
--------------------------
Final Ensemble Information
--------------------------
input file name : crest_rotamers_3.xyz
output file name : crest_rotamers_4.xyz
number of atoms : 20
number of points on xyz files : 162
RMSD threshold : 0.1250
Bconst threshold : 0.0100
population threshold : 0.0500
# fragment in coord : 1
# bonds in reference structure : 19
number of reliable points : 162
sorting energy window (EWIN) : 6.0000 / kcal*mol⁻¹
reference state Etot : -33.884835140000000
number of doubles removed by rot/RMSD : 45
total number unique points considered further : 117
Erel/kcal Etot weight/tot conformer set degen origin
1 0.000 -33.88484 0.06131 0.30454 1 5
2 0.004 -33.88483 0.06088
3 0.005 -33.88483 0.06083
4 0.005 -33.88483 0.06081
5 0.006 -33.88483 0.06071
6 0.195 -33.88452 0.04409 0.13066 2 3
7 0.206 -33.88451 0.04329
8 0.206 -33.88451 0.04328
9 0.580 -33.88391 0.02307 0.06891 3 3
10 0.583 -33.88391 0.02293
11 0.584 -33.88391 0.02291
12 0.618 -33.88385 0.02161 0.06482 4 3
13 0.618 -33.88385 0.02161
14 0.619 -33.88385 0.02160
15 0.883 -33.88343 0.01384 0.01384 5 1
16 0.884 -33.88343 0.01381 0.02751 6 2
17 0.888 -33.88342 0.01370
18 0.899 -33.88340 0.01346 0.04036 7 3
19 0.899 -33.88340 0.01346
20 0.900 -33.88340 0.01344
21 0.951 -33.88332 0.01233 0.02462 8 2
22 0.953 -33.88332 0.01229
23 1.026 -33.88320 0.01087 0.03260 9 3
24 1.026 -33.88320 0.01087
25 1.026 -33.88320 0.01087
26 1.128 -33.88304 0.00915 0.01829 10 2
27 1.128 -33.88304 0.00915
28 1.137 -33.88302 0.00900 0.00900 11 1
29 1.141 -33.88302 0.00894 0.02674 12 3
30 1.143 -33.88301 0.00892
31 1.146 -33.88301 0.00887
32 1.147 -33.88301 0.00886 0.02657 13 3
33 1.148 -33.88301 0.00885
34 1.148 -33.88301 0.00885
35 1.159 -33.88299 0.00869 0.02605 14 3
36 1.159 -33.88299 0.00868
37 1.159 -33.88299 0.00868
38 1.162 -33.88298 0.00863 0.02543 15 3
39 1.179 -33.88296 0.00840
40 1.179 -33.88296 0.00840
41 1.245 -33.88285 0.00751 0.02252 16 3
42 1.245 -33.88285 0.00751
43 1.245 -33.88285 0.00751
44 1.380 -33.88264 0.00598 0.01794 17 3
45 1.380 -33.88264 0.00598
46 1.380 -33.88264 0.00598
47 1.496 -33.88245 0.00492 0.01472 18 3
48 1.498 -33.88245 0.00490
49 1.498 -33.88245 0.00490
50 1.519 -33.88241 0.00473 0.00943 19 2
51 1.523 -33.88241 0.00470
52 1.557 -33.88235 0.00443 0.02655 20 6
53 1.558 -33.88235 0.00443
54 1.559 -33.88235 0.00442
55 1.559 -33.88235 0.00442
56 1.559 -33.88235 0.00442
57 1.560 -33.88235 0.00442
58 1.578 -33.88232 0.00429 0.01285 21 3
59 1.578 -33.88232 0.00429
60 1.579 -33.88232 0.00428
61 1.613 -33.88227 0.00404 0.00404 22 1
62 1.679 -33.88216 0.00361 0.00722 23 2
63 1.680 -33.88216 0.00361
64 1.960 -33.88171 0.00225 0.00225 24 1
65 1.996 -33.88165 0.00212 0.00635 25 3
66 1.996 -33.88165 0.00212
67 1.996 -33.88165 0.00212
68 2.012 -33.88163 0.00206 0.01023 26 5
69 2.014 -33.88163 0.00205
70 2.018 -33.88162 0.00204
71 2.019 -33.88162 0.00204
72 2.019 -33.88162 0.00204
73 2.052 -33.88157 0.00193 0.00574 27 3
74 2.054 -33.88156 0.00192
75 2.061 -33.88155 0.00190
76 2.121 -33.88146 0.00171 0.00511 28 3
77 2.126 -33.88145 0.00170
78 2.129 -33.88144 0.00169
79 2.226 -33.88129 0.00144 0.00144 29 1
80 2.561 -33.88075 0.00082 0.00245 30 3
81 2.562 -33.88075 0.00082
82 2.562 -33.88075 0.00081
83 2.587 -33.88071 0.00078 0.00233 31 3
84 2.590 -33.88071 0.00078
85 2.591 -33.88071 0.00078
86 2.595 -33.88070 0.00077 0.00231 32 3
87 2.595 -33.88070 0.00077
88 2.595 -33.88070 0.00077
89 2.711 -33.88051 0.00063 0.00127 33 2
90 2.713 -33.88051 0.00063
91 2.713 -33.88051 0.00063 0.00063 34 1
92 3.109 -33.87988 0.00032 0.00065 35 2
93 3.109 -33.87988 0.00032
94 3.177 -33.87977 0.00029 0.00086 36 3
95 3.177 -33.87977 0.00029
96 3.181 -33.87977 0.00029
97 3.256 -33.87965 0.00025 0.00025 37 1
98 3.263 -33.87964 0.00025 0.00050 38 2
99 3.268 -33.87963 0.00025
100 3.282 -33.87961 0.00024 0.00048 39 2
101 3.284 -33.87960 0.00024
102 3.309 -33.87956 0.00023 0.00069 40 3
103 3.310 -33.87956 0.00023
104 3.317 -33.87955 0.00023
105 3.337 -33.87952 0.00022 0.00022 41 1
106 3.537 -33.87920 0.00016 0.00047 42 3
107 3.538 -33.87920 0.00016
108 3.539 -33.87919 0.00016
109 3.819 -33.87875 0.00010 0.00019 43 2
110 3.829 -33.87873 0.00010
111 3.835 -33.87872 0.00010 0.00010 44 1
112 3.868 -33.87867 0.00009 0.00018 45 2
113 3.868 -33.87867 0.00009
114 4.453 -33.87774 0.00003 0.00007 46 2
115 4.460 -33.87773 0.00003
116 4.890 -33.87704 0.00002 0.00002 47 1
117 5.517 -33.87604 0.00001 0.00001 48 1
T /K : 298.15
E lowest : -33.88484
ensemble average energy (kcal) : 0.662
ensemble entropy (J/mol K, cal/mol K) : 32.493 7.766
ensemble free energy (kcal/mol) : -2.315
population of lowest in % : 30.454
number of unique conformers for further calc 48
list of relative energies saved as "crest.energies"
-----------------
Wall Time Summary
-----------------
CREST runtime (total) 0 d, 0 h, 4 min, 19.861 sec
------------------------------------------------------------------
Trial metadynamics (MTD) ... 0 min, 1.144 sec ( 0.440%)
Metadynamics (MTD) ... 1 min, 4.245 sec ( 24.723%)
Geometry optimization ... 2 min, 49.998 sec ( 65.419%)
Molecular dynamics (MD) ... 0 min, 7.779 sec ( 2.994%)
Genetic crossing (GC) ... 0 min, 16.568 sec ( 6.376%)
I/O and setup ... 0 min, 0.127 sec ( 0.049%)
------------------------------------------------------------------
* wall-time: 0 d, 0 h, 4 min, 19.861 sec
* cpu-time: 0 d, 0 h, 16 min, 30.037 sec
* ratio c/w: 3.810 speedup
------------------------------------------------------------------
* Total number of energy+grad calls: 155900
CREST terminated normally.
Tip: 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.
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.
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.