AMBER Archive (2007)Subject: Re: AMBER: Umbrella sampling
From: Jerome.GOLEBIOWSKI_at_unice.fr
Date: Mon Feb 12 2007  03:33:18 CST
Hi, did you try to read what Richard Lavery made some years ago ?
maybe it could help.
E. STOFER, C. CHIPOT and R. LAVERY
Free energy calculations of WatsonCrick base pairing in aqueous
solution
J. Am. Chem. Soc. 121, 1999, 95039508
In the context of a nucleic acid, base staking is crucial to keep a
correct angle beteen interacting pairs. Maybe you should consider puting
a restaint on the dihedral between the NA bases.
Starting with a bent structure is probably not relevant if you intend to
draw conclusions for a NA.
Cheers.
Jerome
> Dear Amber users,
>
> I am trying to determine the delta_G of different types of base pairs by
> using umbrella sampling with Amber 9.
> Each system under study consists of a single isolated base pair (e.g.
> AU or CG etc...) surrounded by explicit water molecules (octahedral
> TIP3PBOX 8.0 A).
> I designed a protocol to carry out umbrella sampling calculations.
> Nevertheless I kindly request you to give me your critical point of view
> on the correctness of this protocol and answer a couple of questions.
> AU base pair will be used as an example.
>
> On Step1: I minimized the water molecule and the counter ions (Na+) by
> holding the AU base pair fixed
>
> &cntrl
>
> imin = 1,
>
> maxcyc = 1000,
>
> ncyc = 500,
>
> ntb = 1,
>
> ntr = 1,
>
> cut = 10
>
> /
>
> Hold the base pair fixed
>
> 500.0
>
> RES 1 2
>
> END
>
> END
>
> Step2: the entire system (base pair + water + ions) is minimized
>
> &cntrl
>
> imin = 1,
>
> maxcyc = 2500,
>
> ncyc = 1000,
>
> ntb = 1,
>
> ntr = 0,
>
> cut = 10
>
> /
>
> Step3: equilibration of the system from 0 to 300 K for 5ps. This MD is
> done with weak positional restraints on the base pair during 5ps:
>
> &cntrl
>
> imin = 0,
>
> irest = 0,
>
> ntx = 1,
>
> ntb = 1,
>
> cut = 10,
>
> ntr = 1,
>
> ntc = 2,
>
> ntf = 2,
>
> tempi = 0.0,
>
> temp0 = 300.0,
>
> ntt = 3,
>
> gamma_ln = 2.0,
>
> nstlim = 5000, dt = 0.001
>
> ntpr = 100, ntwx = 100, ntwr = 1000
>
> /
>
> Keep base pair fixed with weak restraints
>
> 10.0
>
> RES 1 2
>
> END
>
> END
>
> Step 4: Equilibration at 300 K of the system during 40 ps
>
> &cntrl
>
> imin = 0, irest = 1, ntx = 7,
>
> ntb = 2, pres0 = 1.0, ntp = 1,
>
> taup = 2.0,
>
> cut = 10, ntr = 0,
>
> ntc = 2, ntf = 2,
>
> tempi = 300.0, temp0 = 300.0,
>
> ntt = 3, gamma_ln = 2.0,
>
> nstlim = 40000, dt = 0.001,
>
> ntpr = 100, ntwx = 100, ntwr = 1000
>
> /
>
> The system effectively reached equilibrium at the end of this
> simulation. However the base pair is not planar anymore and the two
> aromatic rings formed an angle of ~ 160 deg. Thus the AU base is
> slightly bent and as a result the C1ÿC1ÿ distance between the base is
> reduced by ~1 A (angstrom) and measured ~ 9.78 A instead of ~ 10.75 A
> found in the minimized conformation. This could be explained by the
> absence of base stacking in the system.
>
> My plan is to start the umbrella sampling simulation after the
> equilibration step 4 and use the C1ÿC1ÿ distance as the coordinate to
> be used to determined the PMF. Although the C1ÿC1ÿ is altered after
> step 4, should the umbrella sampling computation be started from this
> bent conformation or from the optimized conformation (i.e. start doing
> umbrella sampling after step 3)?
>
> My guess is if I want to skip the equilibrium step 4 I should use
> implicit water solvent and start the umbrella sampling just after a
> minimization step. However would it be advisable to work with implicit
> water solvent in the case of this particular system (AU base pair)?
>
> Is it better to use the distance between the center of mass of each
> molecule instead of C1ÿC1ÿ distance?
>
> An example of an MD simulation input file used for the umbrella sampling
> is showed bellow:
>
> &cntrl
>
> imin = 0, irest = 1, ntx = 7,
>
> ntb = 2, pres0 = 1.0, ntp = 1,
>
> taup = 2.0,
>
> cut = 10, ntr = 0,
>
> ntc = 2, ntf = 2,
>
> tempi = 300.0, temp0 = 300.0,
>
> ntt = 3, gamma_ln = 2.0,
>
> nstlim = 1000, dt = 0.0005,
>
> ntpr = 100, ntwx = 100, ntwr = 100
>
> /
>
> &wt type=ÿDUMPFREQÿ, istep1=10 /
>
> &wt type=ÿENDÿ /
>
> DISANG=dist.RST
>
> DUMPAVE=dist_vs_2
>
> Where the dist.RST files contains:
>
> # distance restraint between A C1ÿ and U C1ÿ
>
> &rst iat=11,44, r1=0., r2=2., r3=2., r4=20., rk2 = 20.,
>
> rk3 = 20., /
>
> I will use 20 windows with 100 points collected for each (2000 points in
> total). The time of the simulation is 0.5 ps.
>
> Is there any optimal time to be used for umbrella sampling? If yes,
> where could I find the method to determine this optimization?
>
> Which method should be used to choose the best rk2/rk3 values?
>
> I thank you in advance for your replies.
>
> Regards,
>
> Franck
>
>
>
> 
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Jerome Golebiowski, PhD
Lab. Chemistry of Bioactive Molecules and Aromas,
Team Chemometrics and Molecular Modeling
University of Nice, parc Valrose
06108 Nice Cedex2 France
tel : +33 (0)4 92 07 61 03
http://www.unice.fr/lcmba
http://www.unice.fr/lcmba/golebiowski

The AMBER Mail Reflector
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