Hello,
I am currently performing molecular dynamics simulations of a
siRNA-protein complex using the OL3-ff19SB force field combination with
the TIP3P water model. The 21-mer siRNA sequence used in the study is as
follows:
_AAUAUCUCGUUCUUGUGACAA_
_UUAUAGAGCAAGAACACUGUU_
While analysing the trajectory from the production run, I observed that
the Watson-Crick base pairing remains stable only up to the 17th base
pair. Beyond this point (i.e., after the 17-mer), the base pairing is
not maintained consistently, and the hydrogen bonds between the
corresponding bases are frequently disrupted throughout the simulation.
I have attached the input files from all stages of the MD simulation for
your reference. I would appreciate any insights or suggestions you might
have regarding this instability issue. Thank you.
Step1:Minimize water and ions
&cntrl
imin=1, maxcyc=20000, ncyc=15000,
cut=10.0,
ntb=1,
ntr=1,
restraint_wt=10.0,
restraintmask='!:WAT & !:Na+ & !:Cl-',
/
Step2:Unrestrained minimization
imin=1, maxcyc=30000, ncyc=25000,
cut=10.0,
ntb=1,
ntr=0,
/
Step-3:Relax water
LET WATER MOVE
&cntrl
timlim = 999999., nmropt = 0, imin = 0,
ntx = 1, irest = 0, ntrx = 1, ntxo = 1,
ntpr = 500, ntwx = 500, ntwv = 0, ntwe = 0,
ntwr = 500,
ntf = 2, ntb = 2,
cut = 10.0, nsnb = 20,
nstlim = 50000, nscm = 2500, iwrap = 1,
t = 0.0, dt = 0.002,
temp0 = 300.0, tempi = 200.0, tautp=0.5,
ntt = 1,
ntp =1 , taup = 1.0,
ntc = 2, tol = 0.00001,
ibelly=0, ntr=1,
restraintmask=':1-873' , restraint_wt=10.0,
&end
/
Step-4:heat NPT 0.5 ns
Heating System
&cntrl
imin=0, nmropt=1,
ntx=1, irest=0,
ntpr=500, ntwr=500, ntwx=500, iwrap=1,
ntf=2, ntb=1, cut=10.0, nsnb=20,
igb=0,
ibelly=0, ntr=1,
nstlim=250000, nscm=500, dt=0.002,
ntt=1, temp0=300.0, tempi=0.0, tautp=0.5
ntc=2,restraintmask=':1-873',
restraint_wt=100,
&end
&wt type='REST', istep1=0, istep2=0, value1=1.0, value2=1.0, &end
&wt type='TEMP0', istep1=0, istep2=250000, value1=0.0, value2=300, &end
&wt type='END' &end
/
Step-5:Density Equilibration
&cntrl
imin=0, nstlim=250000, dt=0.002,
irest=1, ntx=5,
ntc=2, ntf=2, ntb=2, ntp=1, taup=1.0,
cut=8.0, iwrap=1, ig=-1,
ntpr=10000, ntwx=10000, ntwr=10000,
ntt=3, gamma_ln=5.0, temp0=300.0,
ntr=1, restraintmask=':1-873', restraint_wt=20.0,
ioutfm=1, barostat=2,
/
Step-6:MD1 simulation backbone restrained
&cntrl
imin=0, nstlim=100000, dt=0.002,
irest=1, ntx=5,
ntc=2, ntf=2, ntb=1,
cut=8.0, iwrap=1, ig=-1,
ntpr=500, ntwx=500, ntwr=500,
ntt=3, gamma_ln=5.0, temp0=300.0,
ntr=1,
restraintmask="(:1-838 & .CA,C,N,O) | (:839) | (:840 &
.P2,O9,O10,O12,O4,O2,C5,C3,C1) | (:841-873 &
.P,OP1,OP2,O3',O5',C3',C4',C5')",
restraint_wt=10.0,
ioutfm=1,
/
Step-7:MD1 simulation backbone restrained
&cntrl
imin=0, nstlim=100000, dt=0.002,
irest=1, ntx=5,
ntc=2, ntf=2, ntb=1,
cut=8.0, iwrap=1, ig=-1,
ntpr=500, ntwx=500, ntwr=500,
ntt=3, gamma_ln=5.0, temp0=300.0,
ntr=1,
restraintmask="(:1-838 & .CA,C,N,O) | (:839) | (:840 &
.P2,O9,O10,O12,O4,O2,C5,C3,C1) | (:841-873 &
.P,OP1,OP2,O3',O5',C3',C4',C5')",
restraint_wt=5.0,
ioutfm=1,
/
Step-8:MD1 simulation backbone restrained
&cntrl
imin=0, nstlim=100000, dt=0.002,
irest=1, ntx=5,
ntc=2, ntf=2, ntb=1,
cut=8.0, iwrap=1, ig=-1,
ntpr=500, ntwx=500, ntwr=500,
ntt=3, gamma_ln=5.0, temp0=300.0,
ntr=1,
restraintmask="(:1-838 & .CA,C,N,O) | (:839) | (:840 &
.P2,O9,O10,O12,O4,O2,C5,C3,C1) | (:841-873 &
.P,OP1,OP2,O3',O5',C3',C4',C5')",
restraint_wt=1.0,
ioutfm=1,
/
Step-9:MD1 simulation backbone restrained
&cntrl
imin=0, nstlim=100000, dt=0.002,
irest=1, ntx=5,
ntc=2, ntf=2, ntb=1,
cut=8.0, iwrap=1, ig=-1,
ntpr=500, ntwx=500, ntwr=500,
ntt=3, gamma_ln=5.0, temp0=300.0,
ntr=1,
restraintmask="(:1-838 & .CA,C,N,O) | (:839) | (:840 &
.P2,O9,O10,O12,O4,O2,C5,C3,C1) | (:841-873 &
.P,OP1,OP2,O3',O5',C3',C4',C5')",
restraint_wt=0.25,
ioutfm=1,
/
Step-10:MD1 simulation backbone restrained
&cntrl
imin=0, nstlim=100000, dt=0.002,
irest=1, ntx=5,
ntc=2, ntf=2, ntb=1,
cut=8.0, iwrap=1, ig=-1,
ntpr=500, ntwx=500, ntwr=500,
ntt=3, gamma_ln=5.0, temp0=300.0,
ntr=0,
ioutfm=1,
/
Step-11:good energy conservation, 2fs.
&cntrl
ntx=5, irest=1,
ntc=2, ntf=2, tol=0.000001,
nstlim=250000000,
ntpr=1000, ntwx=1000,
ntwr=10000,
dt=0.002, cut=8.0,
ntt=0, ntb=1, ntp=0, ntr=0,
ioutfm=1,
/
&ewald
dsum_tol=0.000001,
/
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Received on Wed May 14 2025 - 04:30:01 PDT
