Supporting Information: Improved Force Field Parameters

Lead to a Better Description of RNA Structure

Christina Bergonzo, Thomas E. Cheatham III*

Department of Medicinal Chemistry, College of Pharmacy, University of Utah, Salt Lake City,
Utah 84112, United States

Contents  
Supporting Figure 1: r(GACC) population histogram analysis for AMBER ff12(top) and
AMBER ff12 + vdWbb (bottom). ..................................................................................................... 2  
Supporting Table 1: Ratio of NMR major to NMR minor in each force field/water model
combination ..................................................................................................................................... 3  
Supporting Figure 2: r(CCCC) population histogram analysis for AMBER ff12(top) and
AMBER ff12 + vdWbb (bottom). ..................................................................................................... 4  
Supporting Table 2: Timing Data for three and four point water models for r(GACC) ............... 5  
Supporting Figure 3a: Cluster Population Correlation Plots for three point water model M-
REMD simulations using ff12 and ff12 + vdWbb ............................................................................ 6  
Supporting Figure 3b: Cluster Population Correlation Plots for four point water model M-
REMD simulations using ff12 and ff12 + vdWbb ............................................................................ 7  
Supporting Text: Simulation Details ............................................................................................. 8  
Supporting CPPTRAJ Script: Clustering command for analysis of GACC tetranucleotide
simulations. ...................................................................................................................................... 9  
Supporting CPPTRAJ Script: Clustering command for analysis of CCCC tetranucleotide
simulations. ...................................................................................................................................... 9  
Supporting File: Frcmod.vdW – force modification file for building ff12 + vdWall
modifications. .................................................................................................................................. 9  
Supporting File: Parmed.py script for modifying O4’ atom from ff12 + vdWall to default ff12,
generating ff12 + vdWbb modifications. .......................................................................................... 9  

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Supporting  Figure  1:  r(GACC)  population  histogram  analysis  for  

AMBER  ff12(top)  and  AMBER  ff12  +  vdWbb  (bottom).      

Bottom plot is identical to Figure 1 from the main text and is reproduced here to allow direct
comparison.

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Supporting  Table  1:  Ratio  of  NMR  major  to  NMR  minor  in  each  
force  field/water  model  combination  

Force Field Water Model Ratio NMR major:NMR minor

Experiment 3:1
ff12 TIP3P 0.85:1
SPC/E 0.87:1
TIP4PEw 1.1:1
OPC 1.6:1
ff12 + vdWbb TIP3P 1.8:1
SPC/E 1.7:1
TIP4PEw 2.5:1
OPC 3.2:1

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Supporting  Figure  2:  r(CCCC)  population  histogram  analysis  for  
AMBER  ff12(top)  and  AMBER  ff12  +  vdWbb  (bottom).      

Bottom plot is identical to Figure 2 from the main text and is reproduced here to allow direct
comparison.

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Supporting  Table  2:  Timing  Data  for  three  and  four  point  water  
models  for  r(GACC)  

Model Timing in Amber14 pmemd.cuda.MPI,

hydrogen mass repartitioned (4 fs time step)
SPC/E 305 ns/day
OPC 220 ns/day

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Supporting  Figure  3a:  Cluster  Population  Correlation  Plots  for  
three  point  water  model  M-­‐REMD  simulations  using  ff12  and  ff12  +  
vdWbb  

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Supporting  Figure  3b:  Cluster  Population  Correlation  Plots  for  four  
point  water  model  M-­‐REMD  simulations  using  ff12  and  ff12  +  vdWbb  

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Supporting  Text:  Simulation  Details  

r(GACC) was built in an A-form conformation and solvated with either TIP3P, SPC/E,

TIP4PEw, or OPC water using tLeap. r(CCCC) was built in a random conformation and solvated

with either TIP3P or OPC water using tLeap. Each system was neutralized with three Na+ ions

using the Joung-Cheatham ion parameters1 optimized for the water model used to explicitly

solvate the tetranucleotide with 2497 water molecules. For the OPC model we used TIP4PEw

ion parameters, as recommended in the Amber14 manual. Hydrogen masses of the solute were

repartitioned to 3.07 a.u. using parmed.py and allowing use of a 4 fs time step for production

dynamics.2 M-REMD simulations were performed as described previously, combining

temperature and scaled dihedral force constant Hamiltonian dimensions, totaling 192 replicas,

where each replica ran on its own GPU.3

(1) Joung, I. S.; Cheatham 3rd, T. E. J. Phys. Chem. B 2008, 112, 9020.

(2) Hopkins, C. W.; Le Grand, S.; Walker, R. C.; Roitberg, A. E. J. Chem. Theory Comput.
2015, 11, 1864.

(3) Bergonzo, C.; Henriksen, N. M.; Roe, D. R.; Swails, J. M.; Roitberg, A. E.; Cheatham 3rd,
T. E. J. Chem. Theory Comput. 2014, 10, 492.

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Supporting  CPPTRAJ  Script:  Clustering  command  for  analysis  of  
GACC  tetranucleotide  simulations.  
parm ../../nowat.GACC.parm7
trajin ../nowat.nc.0
#Set sieve so there are 10,000 frames during 1st pass
cluster dbscan minpoints 25 epsilon 0.9 \
rms :1@N2,O6,C1',P,:2@H2,N6,C1',P,:3@O2,H5,C1',P,:4@O2,H5,C1',P \
sievetoframe sieve 3 out cvt.dat summary summary.dat \
repout rep repfmt pdb cpopvtime cpop.agr normframe

Supporting  CPPTRAJ  Script:  Clustering  command  for  analysis  of  

CCCC  tetranucleotide  simulations.  
parm ../../nowat.CCCC.parm7
trajin ../nowat.nc.0
#Set sieve so there are 10,000 frames during 1st pass
cluster dbscan minpoints 25 epsilon 0.5 \
rms :1-4@O2,H5,C1',P \
sievetoframe sieve 3 out cvt.dat summary summary.dat \
repout rep repfmt pdb cpopvtime cpop.agr normframe

Supporting  File:  Frcmod.vdW  –  force  modification  file  for  building  

ff12  +  vdWall  modifications.  
Steinbrecher-Latzer-Case Phosphate Oxygen parameters (JCTC, 8,
4405-12, 2012)

MASS
O2 16.00 0.434
OS 16.00 0.465

NONB
O2 1.7493 0.2100
OS 1.7718 0.1700

Supporting  File:  Parmed.py  script  for  modifying  O4’  atom  from  ff12  
+  vdWall  to  default  ff12,  generating  ff12  +  vdWbb  modifications.  
addLJType @O4' radius 1.6837 epsilon 0.1700
parmout ff12vdWbb.parm7
go