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Simulation report and files

General information

Name: DESRES-ANTON-10931493 2 µs simulation of an investigational or FDA approved drug molecule binding to a construct of the SARS-CoV-2 trimeric spike protein, no water or ions (lomibuvir)

Included proteins: Spike

Uniprot ID: P0DTC2

Species: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) (SARS-CoV-2)

PDB ID: 6VXX

Description: This simulation is part of a series of 50 simulations: 50 2 µs trajectories of FDA approved or investigational drug molecules that in simulation remained bound to a construct of the SARS-CoV-2 trimeric spike protein at positions that might conceivably allosterically disrupt the interaction between these proteins. The small molecule drugs and their initial binding poses were chosen from a combination of molecular dynamics simulation and docking performed using an FDA-investigational drug library. The 50 putative spike protein binding small molecules located at three regions on the spike trimer, a pocket in the RBD whose formation may possibly enhance RBD-RBD interactions in the closed conformation (8 molecules), a pocket between the two RBDs in the closed conformation (29 molecules), and a pocket that involves three RBDs in the closed conformation (13 molecules). The simulations used the Amber ff99SB-ILDN force field for proteins, the CHARMM TIP3P model for water, and the generalized Amber force field for small molecules. The C- and N-peptide termini were capped with amide and acetyl groups respectively. The spike trimer construct was modeled from PDB entries 6VXX and 6VW1, only retaining the RBD and a short region from S1 fusion protein as a minimal system for maintaining a trimer assembly. The system was neutralized and salted with NaCl, with a final concentration of 0.15 M. The interval between frames is 1.2 ns. The simulations were conducted at 310 K in the NPT ensemble.

Extracted from: BioExcel (ID: MCV1900171)

Author: D. E. Shaw Research

Submission date: October 22, 2020

System setup

Ligands:

lomibuvir

Membrane composition: None

Solvent type: TIP3P (water was filtered out of the simulation output)

Total number of atoms: 14520

Simulation details

Software and version: Anton supercomputer specific tools None

Forcefield and version: Amber ff99SB-ILDN

Delta : 1.2 ns

Replicates: 1

Accumulated simulation time: 2.0016 µs



References

D. E. Shaw Research. Molecular Dynamics Simulations Related to SARS-CoV-2. D. E. Shaw Research Technical Data, 2020. http://www.deshawresearch.com/resources_sarscov2.html/


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The interaction network has been generated using Flare Plots, powered by R. Fonseca and A. J. Venkatakrishnan.

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DESRES-ANTON-10931493 2 µs simulation of an investigational or FDA approved drug molecule binding to a construct of the SARS-CoV-2 trimeric spike protein, no water or ions (lomibuvir) ( 6VXX)

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Variant impact

Select a variant from the sequence to obtain its impact score as well as mutation effect and time-dependent descriptors:

Display isolate: All isolates
Spike
AA
Seq. pos.
PDB resID
N
331
331
I
332
332
T
333
333
N
334
334
L
335
335
C
336
336
P
337
337
F
338
338
G
339
339
E
340
340
V
341
341
F
342
342
A
344
344
T
345
345
R(K)
346
346
F
347
347
A(P)
348
348
S
349
349
V
350
350
Y
351
351
A
352
352
W
353
353
N(E)
354
354
R
355
355
K
356
356
R(K)
357
357
I
358
358
S
359
359
N
360
360
C
361
361
V
362
362
A
363
363
D
364
364
Y
365
365
S
366
366
V
367
367
L
368
368
Y
369
369
N
370
370
S
371
371
A(T)
372
372
S(F)
373
373
F
374
374
S
375
375
T
376
376
F
377
377
K
378
378
C
379
379
Y
380
380
G
381
381
V
382
382
S
383
383
P(A)
384
384
T
385
385
K
386
386
L
387
387
N
388
388
D
389
389
L
390
390
C
391
391
F
392
392
T(S)
393
393
N
394
394
V
395
395
Y
396
396
A
397
397
D
398
398
S
399
399
F
400
400
V
401
401
I(V)
402
402
R(K)
403
403
G
404
404
D
405
405
E(D)
406
406
V
407
407
R
408
408
Q
409
409
I
410
410
A
411
411
P
412
412
G
413
413
Q
414
414
T
415
415
G
416
416
K(V)
417
417
I
418
418
A
419
419
D
420
420
Y
421
421
N
422
422
Y
423
423
K
424
424
L
425
425
P
426
426
D
427
427
D
428
428
F
429
429
T(M)
430
430
G
431
431
C
432
432
V
433
433
I(L)
434
434
A
435
435
W
436
436
N
437
437
S(T)
438
438
N(R)
439
439
N
440
440
L(I)
441
441
D
442
442
S
443
445
K(T)
444
446
G
447
447
N
448
448
Y
449
449
N
450
450
Y
451
453
L
452
455
Y(F)
453
456
R
457
457
K
462
462
P
463
463
F
464
464
E
465
465
R
466
466
D
467
467
I
472
472
Y
489
489
F
490
490
P
491
491
L
492
492
Q
493
493
S
494
494
Y
495
495
G
496
496
F
497
497
Q
498
498
P
499
499
T
500
500
N
501
501
V
503
503
G
504
504
Y
505
505
Q
506
506
P
507
507
Y
508
508
R
509
509
V
510
510
V
511
511
V
512
512
L
513
513
S
514
514
F
515
515
E
516
516
L
517
517
L
518
518
H(N)
519
519
A
520
520
P
521
521
A
522
522
T
523
523
V
524
524
C
525
525
G
526
526
P
527
527
S
730
730
M
731
731
T
732
732
K
733
733
T
734
734
S
735
735
V
736
736
D
737
737
C
738
738
T
739
739
M
740
740
Y
741
741
I
742
742
C
743
743
G
744
744
D
745
745
S
746
746
T
747
747
E
748
748
C
749
749
S
750
750
N
751
751
L
752
752
L
753
753
L
754
754
Q
755
755
Y
756
756
G
757
757
S
758
758
F
759
759
C
760
760
T
761
761
Q
762
762
L
763
763
N
764
764
R
765
765
A
766
766
L
767
767
T
768
768
G
769
769
I
770
770
A
771
771
V
772
772
D
775
950
V
781
951
V
785
952
N
801
953
Q
804
954
N
824
955
A
871
956
Q
872
957
A
876
958
L
877
959
N
907
960
T
912
961
L
916
962
V
951
963
K
964
964
Q
965
965
L
966
966
S
967
967
S
968
968
N
969
969
F
970
970
G
971
971
A
972
972
I
973
973
S
974
974
S
975
975
V
976
976
L
977
977
N
978
978
D
979
979
I
980
980
L
981
981
S
982
982
R
983
983
L
984
984
D
985
985
K(P)
986
986
V(P)
987
987
E
988
988
A
989
989
E
990
990
V
991
991
Q
992
992
I
993
993
D
994
994
R
995
995
L
996
996
I
997
997
T
998
998
G
999
999
R
1000
1000
L
1001
1001
Q
1002
1002
S
1003
1003
L
1004
1004
Q
1005
1005
T
1006
1006
Y
1007
1007
V
1008
1008
T
1009
1009
Q
1010
1010
Q
1011
1011
L
1012
1012
I
1013
1013
R
1014
1014
A
1015
1015
Impact score

Select a variant from the sequence above to obtain its impact score as well as mutation effect and time-dependent descriptors.