Re: Sudden /\A drop in last FEP window

From: Jérôme Hénin (jerome.henin_at_ibpc.fr)
Date: Sat Jul 28 2018 - 08:41:19 CDT

The value of alchVdWShiftCoeff should not change the actual (converged)
value of the free energy difference. Therefore at least one of these was
probably not well-converged. You can track convergence using tools like
ParseFEP.

Jerome

On Sat, 28 Jul 2018 at 12:30, Francesco Pietra <chiendarret_at_gmail.com>
wrote:

> Hi Jerome:
> By only changing alchVdWShiftCoeff from 4.0 to 6.0, your expectation
> was fulfilled. The trend of /\A vs lambda was now smooth
>
> .....................
> ....................
> 0.9000/-12.4193
> 0.9100/-13.8066
> 0.9200/-15.0984
> 0.9300/-16.4011
> 0.9400/-17.5040
> 0.9500/-18.5221
> 0.9600/-19.5255
> 0.9700/-20.5133
> 0.9800/-21.4422
> 0.9900/-22.4359
> 1.0000/-23.6922
>
> I cannot detect any alarming sign in the simulation, in particular, the
> ligand remains undeformed and well in place throughout, not displaced, not
> rotated.
> Therefore, I am now perplexed at the value of /\A, differing by eight
> units from previous FEP with alchVdWShiftCoeff = 4.0.
> On the other hand, twenty windows for a small sector as 0.8-1.0 should not
> be too few.
>
> I would appreciate very much advice. Aas the change of alchVdWShiftCoeff
> from 4.0 to 6.0 too large?
>
> francesco
>
> ---------- Forwarded message ---------
> From: Francesco Pietra <chiendarret_at_gmail.com>
> Date: Fri, Jul 27, 2018 at 10:13 AM
> Subject: Fwd: namd-l: Sudden /\A drop in last FEP window
> To: <jerome.henin_at_ibpc.fr>, NAMD <namd-l_at_ks.uiuc.edu>
>
>
> On these basis I have resubmitted (on the queue) that FEP from scratch, by
> only changing alchVdWShiftCoeff from 4.0 to 6.0. We will see whether
> further changes, as you suggested, are necessary
>
> thanks
>
> francesco
>
> ---------- Forwarded message ---------
> From: Francesco Pietra <chiendarret_at_gmail.com>
> Date: Thu, Jul 26, 2018 at 7:54 PM
> Subject: Re: namd-l: Sudden /\A drop in last FEP window
> To: <jerome.henin_at_ibpc.fr>
> Cc: NAMD <namd-l_at_ks.uiuc.edu>
>
>
> Hi Jerome
> During my jogging I recognized to have missed the prot ocolin my mail. I
> was too late, anyway the protocol follows:
>
> outputenergies 1000
> outputtiming 1000
> outputpressure 1000
> restartfreq 1000
> XSTFreq 1000
> dcdFreq 5000
>
> hgroupcutoff 2.8
> switching on
> switchdist 10.0
> cutoff 12.0
> pairlistdist 14.0
>
> wrapAll on
>
> langevin on
> langevintemp 300.0
> langevindamping 2.0
>
> langevinpiston on
> langevinpistontarget 1
> langevinpistonperiod 100
> langevinpistondecay 100
> langevinpistontemp 300
> StrainRate 0.0 0.0 0.0
> useGroupPressure yes
>
> PME yes
> PMETolerance 10e-6
> PMEInterpOrder 4
> PMEGridSpacing 1
>
> timestep 0.5
> fullelectfrequency 2
> nonbondedfreq 1
>
> rigidbonds water
> stepspercycle 20
>
> alch on
> alchType FEP
> alchFile npt-15_frwd.fep
> alchCol B
> alchOutFile frwd-08.fepout
> alchOutFreq 50
>
> alchVdwLambdaEnd 1.0
> alchElecLambdaStart 0.5
> alchVdWShiftCoeff 4.0
> alchEquilSteps 100000
> set numSteps 400000
>
> runFEP 0.80 1.00 0.01 $numSteps
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
> On Thu, Jul 26, 2018 at 6:48 PM Jérôme Hénin <jerome.henin_at_ibpc.fr> wrote:
>
>> Hi,
>>
>> That is more or less an expected physical effect when the excluded volume
>> due to LJ repulsion disappears. In principle the soft-core potentials were
>> introduced to limit this effect (that is, to spread it over a broader range
>> of lambda and remove the singularity). You can try experimenting with
>> softer soft-core potentials by increasing the value of alchVdwShiftCoeff
>> from its default of 5 Å^2. Just note that the risk with too much softening
>> is to allow atoms of opposite charges to overlap, which leads to an
>> electrostatic catastrophe (singular Coulomb energy). So the goal is to keep
>> the barrier high enough that those clashes don't occur as long as the
>> Coulomb potential is nonzero. If you are using a protocol that separates
>> the contributions entirely, that is alchElecLambdaStart
>> >= alchVdwLambdaEnd, then there is no such risk and I suppose anything goes.
>>
>> Jerome
>>
>> On Thu, 26 Jul 2018 at 17:46, Francesco Pietra <chiendarret_at_gmail.com>
>> wrote:
>>
>>> Hello
>>> With every ligand-receptor FEP that I am carrying out with NAMD2.12, I
>>> noticed a sudden drop in the /\A values when when approaching lambda = 1.0,
>>> which seems to me prone to introducing large errors. I understand what
>>> happens in the system under such conditions, however i wonder whether the
>>> trend is out of the norm because I am missing some control.
>>>
>>> For example, for a ligand-receptor FEP divided into five sectors (in
>>> order to keep the calculations for each sector within 24hr), the
>>> ParseFEP.log for the 0.8-1.0 sector (lambda 0.01, 20 windows) reports
>>> lambda//\A
>>> ......................
>>> ....................
>>> 0.9000/1.2495
>>> 0.9100/1.2395
>>> 0.9200/1.1549
>>> 0.9300/1.0130
>>> 0.9400/0.6102
>>> 0.9500/-0.0087
>>> 0.9600/-1.8900
>>> 0.9700/-3.8335
>>> 0.9800/-6.8530
>>> 0.9900/-10.5326
>>> 1.0000/-15.9730
>>>
>>> Thanks for advice
>>> francesco pietra
>>>
>>

This archive was generated by hypermail 2.1.6 : Fri Dec 06 2019 - 23:20:01 CST