[gmx-users] Re: Free energy calculation question

[Justin A. Lemkul]

Fabian Casteblanco wrote:
> Hello Justin,
> 
> You mean that only for vdW decoupling, you would need to use soft-core
> potentials?  I had soft -core potentials on for decoupling the
> electrostatic interactions (see below).   What would I use in its
> place?  Thanks again for your help!
> 

You only need soft-core for LJ transformations.  Set sc_alpha to 0 (as you have 
noted in the comment) for normal (linear) interpolation.

-Justin

> 
> ;Production MD
> ;------------------------------------------------------------------------------------
> include		=-I/mphase/users2/fabian/CGenff
> title		=CGenFF Lov/Eth Solution MD run
> 
> ;PARAMETERS - describing what to do, when to stop and what to save
> ;------------------------------------------------------------------------------------
> 
> ;Run parameters
> integrator		=sd		;leap-frog integrator
> ld_seed			=-1
> nsteps			=500000		;2*500000=1000ps, 1 ns
> dt			=0.002		;2 fs
> nstcomm                 = 100		;*** - frequency for center of mass
> motion removal
> 
> ;Output control
> nstxout			=1000		;save coordinates every 2ps
> nstvout			=1000		;save velocities every 2 ps
> nstenergy		=1000		;save energies every 2 ps
> nstlog			=1000		;update log file every 2 ps
> nstxtcout		=1000		;xtc compressed trajectory output every 2 ps
> xtc-precision           =1000		;*** - precision to write to xtc trajectory
> 
> ;Bond Parameters
> continuation		=yes		;Restarting after NPT
> constraint_algorithm	=lincs	    	;holonomic constraints
> constraints		=all-bonds  	;all bonds (even heavy atom-H bonds) constr;ained
> lincs_iter		=1	    	;accuracy of LINCS
> lincs_order		=12	    	;also related to accuracy
> 
> ;Neighborhood searching
> ns_type			=grid		;search neighboring grid cells
> nstlist			=5		;#steps.  5*0.002 ps = 5* 2 fs = 10 fs - Frequency to
> update the neighbor list (and the long-range forces, when 					;using
> twin-range cut-off’s). When this is 0, the neighbor list is made only
> once.
> rlist			=1.1		;short-range neighborlist cutoff (in nm)
> rcoulomb		=1.1		;short-range electrostatic cutoff (in nm)
> pbc	  		=xyz		; 3-D PBC
> 
> ;Electrostatics	
> coulombtype		=PME		;Particle Mesh Ewald for long-range electrostat;ics
> pme_order		=4		;cubic interpolation
> fourierspacing		=0.16		;grid spacing for FFT
> 
> ; van der Waals
> vdwtype	    		=Shift     	;Van der Waals for CHARMM
> rvdw_switch 		=0.8
> rvdw	    		=1.0    	;Short-range Van der Waals cut-off
> 
> ;Dispersion correction
> DispCorr    =EnerPres	;account for cut-off vdW scheme
> 
> ;Temperature coupling is on
> tcoupl	     		=V-rescale	;modified Berendsen thermostat
> tc-grps	     		=SYSTEM  	;two coupling groups - more accurate
> tau_t	     		=0.1		;time constant, in ps
> ref_t	     		=298 		;reference temperature, on for each group, in K
> 
> ;Pressure coupling is on
> pcoupl	  =Parrinello-Rahman	;Pressure coupling on in NPT
> pcoupltype			=isotropic	   ;uniform scaling of box vect;ors
> tau_p				=2.0		   ;time constant, in ps
> ref_p				=1.0		   ;reference pressure, in bar
> compressibility			=4.5e-5		   ;isothermal compr of H2O, ba;r^(-1)
> 
> ; Free energy control stuff
> free_energy             = yes		;*** - Indicates we are doing a free
> energy calculation, and that interpolation between the A and B states
> of the 						;chosen molecule (defined below) will occur.
> init_lambda             = 0.0		;*** - Value of λ
> delta_lambda            = 0		;*** - The value of λ can be incremented
> by some amount per timestep (i.e., δλ/δt) in a technique called "slow
> 						;growth." This method can have significant errors associated
> with it, and thus we will make no time-dependent 						;changes to our
> λ values.
> foreign_lambda          = 0.05		;*** - Additional values of λ for
> which ΔH will be written to dhdl.xvg (with frequency nstdhdl). The
> 						;configurations generated in the trajectory at λ = init_lambda
> will have ΔH calculated for these same 						;configurations at all
> values of λ = foreign_lambda.
> sc-alpha                = 0.5		;*** - the soft-core parameter, a value
> of 0 results in linear interpolation of the LJ and Coulomb
> 					;interactions
> sc-power                = 1.0		;*** - the power for lambda in the
> soft-core function, only the values 1 and 2 are supported
> sc-sigma                = 0.3 		;*** - the soft-core sigma for
> particles which have a C6 or C12 parameter equal to zero or a sigma
> 					;smaller than sc_sigma
> couple-moltype          = LOV	  	;*** - name of moleculetype to decouple
> couple-lambda0          = vdw-q		;*** - all interactions are on at lambda=0
> couple-lambda1          = vdw     	;*** - only vdw interactions are on
> at lambda=1
> couple-intramol         = no		;*** - Do not decouple intramolecular
> interactions. That is, the λ factor is applied to only solute-solvent
> 						;nonbonded interactions and not solute-solute nonbonded
> interactions.
> nstdhdl                 = 100		;*** - The frequency with which ∂H/∂λ
> and ΔH are written to dhdl.xvg. A value of 100 would probably suffice,
> since 						;the resulting values will be highly correlated and the
> files will get very large. You may wish to increase this 						;value
> to 100 for your own work.
> 
> ;Velocity generation
> gen_vel	  =no	;Velocity generation is off
> 
> ;END
> 
> On Wed, Aug 31, 2011 at 11:24 AM, Fabian Casteblanco
> <fabian.casteblanco at gmail.com> wrote:
>> Hello Justin,
>>
>> I'm calculating the free energy of a drug in an alcohol solvent.  I
>> have a question referring to your free energy tutorial.  You mentioned
>> that decoupling of electrostatic interactions is linear and decoupling
>> of vdW can vary.  Is this true for your case of methanol in water or
>> for all cases?  When I ran my system of drug in ethanol solvent, I got
>> a non linear dG for both electrostatic and vdW.  Also, is there no
>> need to find dG of cav ( the free energy required to form the solute
>> cavity within the solvent) ?  I have attached some graphs.
>>
>> Thanks for your help.  Your tutorial was extremely useful.
>>
>> --
>> Best regards,
>>
>> Fabian F. Casteblanco
>> Rutgers University --
>> Chemical Engineering PhD Student
>> C: +908 917 0723
>> E:  fabian.casteblanco at gmail.com
>>
> 
> 
> 

-- 
========================================

Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

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