Ligand structure changes after energy minimization using Steep descent algorithm

User discussions
1

GROMACS version: 2019
GROMACS modification: Yes/No
Here post your question
I did energy minimization of my ligand and the em.gro file contained a structure with same no of atoms but different bonds between the carbon atoms. The structure of 6,5-fused bicyclic moiety was completey different. What is the reason

2

Please provide screenshots or coordinate files of the molecule. Note that bonds that you see in visualization software have no meaning; they are guessed by the software itself based on interatomic distances.

Make sure you are not ignoring warnings from grompp about mismatched atom names, as these indicate incompatibility between the coordinates and topology that will lead to problems.

3

image
image1146×464 79.7 KB

My initial structure

4

image
image1146×464 55.9 KB

Final structure

5

Only after energy minimization i got such extra bonds in my ligand. I used Swissparam for generation of ligand topolgy.

6

em.log (879.4 KB)
log file

7

The .log file does not suggest anything particularly useful. Does grompp issue any notes or warnings? The collapse of the five-membered ring into a four-membered ring and the subsequent displacement of one N atom suggests something very wrong with the topology.

8

Hi Professor.
I have not noticed any warnings or notes in the grompp. I am attaching the str file for the ligand.mol2.

  • Toppar stream file generated by
  • CHARMM General Force Field (CGenFF) program version 2.5
  • For use with CGenFF version 4.6

read rtf card append

  • Topologies generated by
  • CHARMM General Force Field (CGenFF) program version 2.5

36 1

! “penalty” is the highest penalty score of the associated parameters.
! Penalties lower than 10 indicate the analogy is fair; penalties between 10
! and 50 mean some basic validation is recommended; penalties higher than
! 50 indicate poor analogy and mandate extensive validation/optimization.

RESI 7L1F 0.000 ! param penalty= 288.500 ; charge penalty= 69.837
GROUP ! CHARGE CH_PENALTY
ATOM P1 PG0 1.476 ! 0.000
ATOM P2 PG0 1.495 ! 0.000
ATOM P3 PG0 1.456 ! 0.000
ATOM O1 OG3C51 -0.631 ! 16.554
ATOM O2 OG311 -0.650 ! 4.977
ATOM O3 OG311 -0.647 ! 0.040
ATOM O4 OG303 -0.636 ! 0.000
ATOM O5 OG304 -0.648 ! 0.000
ATOM O6 OG311 -0.606 ! 0.000
ATOM O7 OG2P1 -0.620 ! 0.000
ATOM O8 OG304 -0.582 ! 0.000
ATOM O9 OG311 -0.630 ! 0.000
ATOM O10 OG2P1 -0.617 ! 0.000
ATOM O11 OG311 -0.644 ! 0.000
ATOM O12 OG311 -0.644 ! 0.000
ATOM O13 OG2P1 -0.632 ! 0.000
ATOM N1 NG2RC0 -0.073 ! 69.837
ATOM N2 NG2R62 -0.475 ! 45.406
ATOM N3 NG2R62 -0.781 ! 28.183
ATOM N4 NG2S3 -0.764 ! 22.006
ATOM C1 CG3C50 0.430 ! 39.691
ATOM C2 CG3C51 0.038 ! 22.458
ATOM C3 CG3C51 0.100 ! 8.792
ATOM C4 CG3C51 0.172 ! 4.373
ATOM C5 CG2R57 0.303 ! 55.431
ATOM C6 CG321 -0.063 ! 0.304
ATOM C7 CG2R57 1.130 ! 48.352
ATOM C8 CG2R51 -0.308 ! 19.354
ATOM C9 CG2RC0 -0.145 ! 53.697
ATOM C10 CG2R51 -0.226 ! 20.406
ATOM C11 CG2R64 0.496 ! 38.049
ATOM C12 CG2R64 0.795 ! 28.027
ATOM N5 NG2R50 -0.692 ! 28.959
ATOM N6 NG2R50 -0.405 ! 10.964
ATOM N7 NG2R51 0.621 ! 19.128
ATOM N8 NG2R50 -0.831 ! 31.323
ATOM H1 HGP1 0.420 ! 0.040
ATOM H2 HGP1 0.420 ! 0.000
ATOM H3 HGP1 0.420 ! 0.000
ATOM H4 HGP1 0.420 ! 0.000
ATOM H5 HGP1 0.420 ! 0.000
ATOM H6 HGP1 0.420 ! 0.000
ATOM H7 HGP4 0.377 ! 0.000
ATOM H8 HGP4 0.377 ! 0.000
ATOM H9 HGA1 0.090 ! 0.723
ATOM H10 HGA1 0.090 ! 0.040
ATOM H11 HGA1 0.090 ! 0.040
ATOM H12 HGA2 0.090 ! 0.000
ATOM H13 HGA2 0.090 ! 0.000
ATOM H14 HGR51 0.188 ! 3.138
ATOM H15 HGR51 0.199 ! 0.376
ATOM H16 HGR62 0.081 ! 15.855
ATOM H17 HGP1 0.246 ! 0.827

BOND P1 O4
BOND P1 O5
BOND P1 O6
BOND P1 O7
BOND P2 O5
BOND P2 O8
BOND P2 O9
BOND P2 O10
BOND P3 O8
BOND P3 O11
BOND P3 O12
BOND P3 O13
BOND O1 C1
BOND O1 C4
BOND O2 C2
BOND O2 H1
BOND O3 C3
BOND O3 H2
BOND O4 C6
BOND O6 H3
BOND O9 H4
BOND O11 H5
BOND O12 H6
BOND N1 N2
BOND N1 C5
BOND N1 C9
BOND N2 C12
BOND N3 C11
BOND N3 C12
BOND N4 C11
BOND N4 H7
BOND N4 H8
BOND C1 C2
BOND C1 C5
BOND C1 C7
BOND C2 C3
BOND C2 H9
BOND C3 C4
BOND C3 H10
BOND C4 C6
BOND C4 H11
BOND C5 C8
BOND C6 H12
BOND C6 H13
BOND C7 N5
BOND C7 N8
BOND C8 C10
BOND C8 H14
BOND C9 C10
BOND C9 C11
BOND C10 H15
BOND C12 H16
BOND N5 N6
BOND N6 N7
BOND N7 N8
BOND N7 H17
IMPR N4 H8 H7 C11
IMPR C11 C9 N3 N4

END

read param card flex append

  • Parameters generated by analogy by
  • CHARMM General Force Field (CGenFF) program version 2.5

! Penalties lower than 10 indicate the analogy is fair; penalties between 10
! and 50 mean some basic validation is recommended; penalties higher than
! 50 indicate poor analogy and mandate extensive validation/optimization.

BONDS
CG2R57 CG3C50 350.00 1.5100 ! 7L1F , from CG2R51 CG3C50, penalty= 15
CG2R57 NG2R50 400.00 1.3800 ! 7L1F , from CG2R51 NG2R50, penalty= 15
CG2R57 NG2RC0 400.00 1.3710 ! 7L1F , from CG2R51 NG2RC0, penalty= 15
CG3C50 CG3C51 195.00 1.5180 ! 7L1F , from CG3C50 CG3C52, penalty= 4
CG3C50 OG3C51 350.00 1.4250 ! 7L1F , from CG3C51 OG3C51, penalty= 6
NG2R62 NG2RC0 420.00 1.3200 ! 7L1F , from NG2R62 NG2R62, penalty= 240

ANGLES
CG2R51 CG2R57 CG3C50 115.00 109.00 ! 7L1F , from CG2R51 CG2R51 CG3C50, penalty= 15
CG2R51 CG2R57 NG2RC0 130.00 108.20 ! 7L1F , from CG2R51 CG2R51 NG2RC0, penalty= 15
CG3C50 CG2R57 NG2R50 170.00 112.00 ! 7L1F , from CG3C52 CG2R52 NG2R50, penalty= 21.2
CG3C50 CG2R57 NG2RC0 170.00 112.00 ! 7L1F , from CG3C52 CG2R52 NG2R50, penalty= 45.2
NG2R50 CG2R57 NG2R50 100.00 111.00 ! 7L1F , from NG2R50 CG2R53 NG2R50, penalty= 43
CG2R51 CG2RC0 CG2R64 130.00 132.00 ! 7L1F , from CG2R51 CG2RC0 CG2R63, penalty= 0.5
CG2R64 CG2RC0 NG2RC0 80.00 118.80 ! 7L1F , from CG2R61 CG2RC0 NG2RC0, penalty= 3
CG2R57 CG3C50 CG2R57 45.00 103.00 ! 7L1F , from CG2R53 CG3C50 CG2RC0, penalty= 10
CG2R57 CG3C50 CG3C51 112.00 102.70 ! 7L1F , from CG2R51 CG3C51 CG3C51, penalty= 6.5
CG2R57 CG3C50 OG3C51 75.00 102.40 ! 7L1F , from CG2R51 CG3C52 OG3C51, penalty= 10.5
CG3C51 CG3C50 OG3C51 45.00 111.10 ! 7L1F , from CG3C51 CG3C51 OG3C51, penalty= 6
CG3C50 CG3C51 CG3C51 58.00 109.50 11.16 2.56100 ! 7L1F , from CG3C51 CG3C51 CG3C51, penalty= 0.8
CG3C50 CG3C51 OG311 75.70 110.10 ! 7L1F , from CG3C51 CG3C51 OG311, penalty= 0.8
CG3C50 CG3C51 HGA1 35.00 111.40 22.53 2.17900 ! 7L1F , from CG3C51 CG3C51 HGA1, penalty= 0.8
CG2R57 NG2R50 NG2R50 110.00 106.80 ! 7L1F , from CG2R51 NG2R50 NG2R50, penalty= 0.5
CG2R57 NG2R50 NG2R51 160.00 103.50 ! 7L1F , from CG2R52 NG2R50 NG2R51, penalty= 2
CG2R64 NG2R62 NG2RC0 65.00 121.00 ! 7L1F , from CG2R64 NG2R62 NG2R62, penalty= 27
CG2R57 NG2RC0 CG2RC0 100.00 109.70 ! 7L1F , from CG2R51 NG2RC0 CG2RC0, penalty= 0.5
CG2R57 NG2RC0 NG2R62 15.00 130.50 ! 7L1F , from CG2R51 NG2RC0 CG2R61, penalty= 45.5
CG2RC0 NG2RC0 NG2R62 15.00 119.80 ! 7L1F , from CG2R61 NG2RC0 CG2RC0, penalty= 45
CG3C50 OG3C51 CG3C51 95.00 111.00 ! 7L1F , from CG3C51 OG3C51 CG3C51, penalty= 0.8

DIHEDRALS
CG2R57 CG2R51 CG2R51 CG2RC0 2.0000 2 180.00 ! 7L1F , from CG2R51 CG2R51 CG2R51 CG2RC0, penalty= 0.5
CG2R57 CG2R51 CG2R51 HGR51 1.5000 2 180.00 ! 7L1F , from CG2R57 CG2R51 CG2R51 HGR52, penalty= 0.5
CG2R51 CG2R51 CG2R57 CG3C50 4.0000 2 180.00 ! 7L1F , from CG2R51 CG2R51 CG2R51 CG3C52, penalty= 16.2
CG2R51 CG2R51 CG2R57 NG2RC0 16.0000 2 180.00 ! 7L1F , from CG2R51 CG2R51 CG2R51 NG2RC0, penalty= 15
HGR51 CG2R51 CG2R57 CG3C50 2.9000 2 180.00 ! 7L1F , from CG3C50 CG2R51 CG2R51 HGR51, penalty= 15
HGR51 CG2R51 CG2R57 NG2RC0 3.7000 2 180.00 ! 7L1F , from NG2RC0 CG2R51 CG2R51 HGR51, penalty= 15
CG2R51 CG2R51 CG2RC0 CG2R64 3.0000 2 180.00 ! 7L1F , from CG2R51 CG2R51 CG2RC0 CG2R63, penalty= 0.5
HGR51 CG2R51 CG2RC0 CG2R64 2.8000 2 180.00 ! 7L1F , from HGR51 CG2R51 CG2RC0 CG2R63, penalty= 0.5
CG2R51 CG2R57 CG3C50 CG2R57 2.0500 3 180.00 ! 7L1F , from CG2R51 CG2R51 CG3C52 CG2R51, penalty= 25.5
CG2R51 CG2R57 CG3C50 CG3C51 0.3500 3 180.00 ! 7L1F , from CG2R51 CG2R51 CG3C51 CG3C51, penalty= 21
CG2R51 CG2R57 CG3C50 OG3C51 0.2800 1 180.00 ! 7L1F , from CG2R51 CG2R51 CG3C52 OG3C51, penalty= 25
CG2R51 CG2R57 CG3C50 OG3C51 0.9800 2 180.00 ! 7L1F , from CG2R51 CG2R51 CG3C52 OG3C51, penalty= 25
CG2R51 CG2R57 CG3C50 OG3C51 1.7500 3 180.00 ! 7L1F , from CG2R51 CG2R51 CG3C52 OG3C51, penalty= 25
NG2R50 CG2R57 CG3C50 CG2R57 3.5000 3 180.00 ! 7L1F , from NG2R50 CG2R52 CG3C52 CG2R51, penalty= 30.5
NG2R50 CG2R57 CG3C50 CG3C51 2.8000 3 180.00 ! 7L1F , from NG2R50 CG2R52 CG3C52 CG3C52, penalty= 30.4
NG2R50 CG2R57 CG3C50 OG3C51 0.2800 1 180.00 ! 7L1F , from CG2R51 CG2R51 CG3C52 OG3C51, penalty= 71.5
NG2R50 CG2R57 CG3C50 OG3C51 0.9800 2 180.00 ! 7L1F , from CG2R51 CG2R51 CG3C52 OG3C51, penalty= 71.5
NG2R50 CG2R57 CG3C50 OG3C51 1.7500 3 180.00 ! 7L1F , from CG2R51 CG2R51 CG3C52 OG3C51, penalty= 71.5
NG2RC0 CG2R57 CG3C50 CG2R57 3.5000 3 180.00 ! 7L1F , from NG2R50 CG2R52 CG3C52 CG2R51, penalty= 54.5
NG2RC0 CG2R57 CG3C50 CG3C51 2.8000 3 180.00 ! 7L1F , from NG2R50 CG2R52 CG3C52 CG3C52, penalty= 54.4
NG2RC0 CG2R57 CG3C50 OG3C51 0.2800 1 180.00 ! 7L1F , from CG2R51 CG2R51 CG3C52 OG3C51, penalty= 73.5
NG2RC0 CG2R57 CG3C50 OG3C51 0.9800 2 180.00 ! 7L1F , from CG2R51 CG2R51 CG3C52 OG3C51, penalty= 73.5
NG2RC0 CG2R57 CG3C50 OG3C51 1.7500 3 180.00 ! 7L1F , from CG2R51 CG2R51 CG3C52 OG3C51, penalty= 73.5
CG3C50 CG2R57 NG2R50 NG2R50 6.5000 2 180.00 ! 7L1F , from CG3C52 CG2R52 NG2R50 CG2R51, penalty= 67.7
CG3C50 CG2R57 NG2R50 NG2R51 3.8000 2 180.00 ! 7L1F , from CG321 CG2R52 NG2R50 NG2R51, penalty= 50
NG2R50 CG2R57 NG2R50 NG2R50 12.5512 2 180.00 ! 7L1F , from NG2R50 CG2R53 NG2R50 NG2R50, penalty= 43
NG2R50 CG2R57 NG2R50 NG2R51 12.0000 2 180.00 ! 7L1F , from NG2R50 CG2R53 NG2R50 NG2R51, penalty= 43
CG2R51 CG2R57 NG2RC0 CG2RC0 9.0000 2 180.00 ! 7L1F , from CG2R51 CG2R51 NG2RC0 CG2RC0, penalty= 15
CG2R51 CG2R57 NG2RC0 NG2R62 3.0000 2 180.00 ! 7L1F , from CG2R51 CG2R51 NG2RC0 CG2R61, penalty= 60
CG3C50 CG2R57 NG2RC0 CG2RC0 0.7000 2 180.00 ! 7L1F , from CG321 CG2R51 NG2RC0 CG2RC0, penalty= 45
CG3C50 CG2R57 NG2RC0 NG2R62 0.7000 2 180.00 ! 7L1F , from CG321 CG2R51 NG2RC0 CG2R61, penalty= 90
NG2R62 CG2R64 CG2RC0 CG2R51 2.2000 2 180.00 ! 7L1F , from NG2R62 CG2R61 CG2RC0 CG2R51, penalty= 15
NG2R62 CG2R64 CG2RC0 NG2RC0 0.0000 2 180.00 ! 7L1F , from NG2R62 CG2R61 CG2RC0 NG2R51, penalty= 38
NG2S3 CG2R64 CG2RC0 CG2R51 1.1583 2 180.00 ! 7L1F , from NG2S3 CG2R61 CG2RC0 CG2R51, penalty= 15
NG2S3 CG2R64 CG2RC0 NG2RC0 0.0000 2 180.00 ! 7L1F , from NG2S3 CG2R64 CG2RC0 NG2R50, penalty= 44
NG2R62 CG2R64 NG2R62 NG2RC0 0.5000 2 180.00 ! 7L1F , from NG2R62 CG2R64 NG2R62 NG2R62, penalty= 27
HGR62 CG2R64 NG2R62 NG2RC0 6.0000 2 180.00 ! 7L1F , from HGR62 CG2R64 NG2R62 NG2R62, penalty= 27
CG2R51 CG2RC0 NG2RC0 CG2R57 8.0000 2 180.00 ! 7L1F , from CG2R51 CG2RC0 NG2RC0 CG2R51, penalty= 0.5
CG2R51 CG2RC0 NG2RC0 NG2R62 1.0000 2 180.00 ! 7L1F , from CG2R51 CG2RC0 NG2RC0 CG2R61, penalty= 45
CG2R64 CG2RC0 NG2RC0 CG2R57 1.0000 2 180.00 ! 7L1F , from CG2R61 CG2RC0 NG2RC0 CG2R51, penalty= 3.5
CG2R64 CG2RC0 NG2RC0 NG2R62 0.8000 2 180.00 ! 7L1F , from CG2R61 CG2RC0 NG2RC0 CG2R61, penalty= 48
CG2R57 CG3C50 CG3C51 CG3C51 0.3400 3 180.00 ! 7L1F , from CG2R51 CG3C51 CG3C51 CG3C51, penalty= 6.5
CG2R57 CG3C50 CG3C51 OG311 0.1400 3 0.00 ! 7L1F , from CG2R51 CG3C51 CG3C51 OG311, penalty= 6.5
CG2R57 CG3C50 CG3C51 HGA1 0.1900 3 0.00 ! 7L1F , from CG2R51 CG3C51 CG3C51 HGA1, penalty= 6.5
OG3C51 CG3C50 CG3C51 CG3C51 0.0000 3 0.00 ! 7L1F , from CG3C51 CG3C51 CG3C51 OG3C51, penalty= 6
OG3C51 CG3C50 CG3C51 OG311 0.2000 3 0.00 ! 7L1F , from OG311 CG3C51 CG3C51 OG3C51, penalty= 6
OG3C51 CG3C50 CG3C51 OG311 0.6000 4 180.00 ! 7L1F , from OG311 CG3C51 CG3C51 OG3C51, penalty= 6
OG3C51 CG3C50 CG3C51 OG311 0.3000 5 0.00 ! 7L1F , from OG311 CG3C51 CG3C51 OG3C51, penalty= 6
OG3C51 CG3C50 CG3C51 OG311 0.5000 6 0.00 ! 7L1F , from OG311 CG3C51 CG3C51 OG3C51, penalty= 6
OG3C51 CG3C50 CG3C51 HGA1 0.1900 3 0.00 ! 7L1F , from OG3C51 CG3C51 CG3C51 HGA1, penalty= 6
CG2R57 CG3C50 OG3C51 CG3C51 0.0000 3 0.00 ! 7L1F , from NG2R51 CG3C51 OG3C51 CG3C51, penalty= 58
CG3C51 CG3C50 OG3C51 CG3C51 0.5000 3 0.00 ! 7L1F , from CG3C51 CG3C51 OG3C51 CG3C51, penalty= 6
CG3C50 CG3C51 CG3C51 CG3C51 0.4100 3 180.00 ! 7L1F , from CG3C51 CG3C51 CG3C51 CG3C51, penalty= 0.8
CG3C50 CG3C51 CG3C51 OG311 0.2000 3 0.00 ! 7L1F , from CG3C51 CG3C51 CG3C51 OG311, penalty= 0.8
CG3C50 CG3C51 CG3C51 HGA1 0.1900 3 0.00 ! 7L1F , from CG3C51 CG3C51 CG3C51 HGA1, penalty= 0.8
CG3C50 CG3C51 OG311 HGP1 0.2900 1 0.00 ! 7L1F , from CG3C51 CG3C51 OG311 HGP1, penalty= 0.8
CG3C50 CG3C51 OG311 HGP1 0.6200 2 0.00 ! 7L1F , from CG3C51 CG3C51 OG311 HGP1, penalty= 0.8
CG3C50 CG3C51 OG311 HGP1 0.0500 3 0.00 ! 7L1F , from CG3C51 CG3C51 OG311 HGP1, penalty= 0.8
CG321 CG3C51 OG3C51 CG3C50 0.3000 3 0.00 ! 7L1F , from CG321 CG3C51 OG3C51 CG3C51, penalty= 0.8
CG3C51 CG3C51 OG3C51 CG3C50 0.5000 3 0.00 ! 7L1F , from CG3C51 CG3C51 OG3C51 CG3C51, penalty= 0.8
HGA1 CG3C51 OG3C51 CG3C50 0.3000 3 0.00 ! 7L1F , from HGA1 CG3C51 OG3C51 CG3C51, penalty= 0.8
CG2R57 NG2R50 NG2R50 NG2R51 14.0000 2 180.00 ! 7L1F , from CG2R51 NG2R50 NG2R50 NG2R51, penalty= 0.5
CG2R57 NG2R50 NG2R51 NG2R50 9.5000 2 180.00 ! 7L1F , from CG2R52 NG2R50 NG2R51 NG2R50, penalty= 2
CG2R57 NG2R50 NG2R51 HGP1 1.4000 2 180.00 ! 7L1F , from CG2R52 NG2R50 NG2R51 HGP1, penalty= 2
CG2R64 NG2R62 NG2RC0 CG2R57 0.5000 2 180.00 ! 7L1F , from CG2R61 NG2R62 NG2R62 CG2R64, penalty= 288.5
CG2R64 NG2R62 NG2RC0 CG2RC0 0.5000 2 180.00 ! 7L1F , from CG2R61 NG2R62 NG2R62 CG2R64, penalty= 281.5

IMPROPERS

END
RETURN

9

Hi Savio,

I don’t know that I can add a huge amount to what Justin said; he knows way more than me, but as somebody who has worked on custom force fields and topologies, I can give a couple pointers.

First, it’s really clear that there’s something deeply wrong in your topology. I would recommend digging into the *.top file that you’re feeding gromacs and look particularly at the centers being affected by the distortion to make certain they’ve been properly assigned.

Second, I would be wary of just using an automatically generated *.top file. The images of the molecules you’ve provided above suggest something like a DNA purine ring system, but there is a questionable assignment that has nitrogen-nitrogen bonding in the ring. Purines don’t have internal azo-linkages and an automated program that is optimized to DNA or protein is probably going to choke trying to assign topology to something like this. I seriously doubt even OPLS would have the appropriate types for this kind of structure; it’s just too strange. If that azo-linkage inside the rings is really what you intend, you probably need to determine your own types. (I’m still trying to wrap my head around the liganding; it seems like it would need a full positive charge on the tertiary amine, making it quaternary in order to deal with the neighboring nitrogen, which is only secondary… is that really what you intend?).

Third, if that bicyclic compound in the picture is actually supposed to be adenine, that’s probably a big part of your problem; that’s not an adenine structure and it won’t be assigned like an adenine.

Good luck!
Greg

10

Hi Greg, The molecule is an analog of Remdesivir which contains a pyrrolo[2,1-f][1,2,4]triazin-4-amine as nucleobase, and thus has that N-N bond you mentioned. How can I make generate parameters for this molecule???