Re: FEP simulations?

From: Christopher Hartshorn (cmhartshorn_at_wsu.edu)
Date: Mon Jan 05 2009 - 03:20:53 CST

Hi Jerome. I have finally gotten my systems to a point where I can
begin to run FEP and I have a few questions.

1) In the paper below, how many steps were performed (eg How much
sampling?) and what is an ideal mix of accuracy and efficiency? I am
using the following FEP parameters to perform a double annihilation of
two simple proteins dimerizing:

fepEquilSteps 1000
set nSteps 10000

set dLambda 0.1

set init {0.0 0.0000001 0.000001 0.00001 0.0001 0.001
0.01 0.05 0.1}
set end {0.9 0.95 0.99 0.999 0.9999 0.99999 0.999999
0.9999999 1.0}

runFEPlist $init $nSteps
runFEP 0.1 0.9 $dLambda $nSteps
runFEPlist $end $nSteps

Too much or too little? or just one of things that needs to be tweaked
until the dG's have little error after x number of steps?

2) This question will tell you that I am still a novice, but why are
rigid bonds required to run the FEP?

Thank you very much for your help.

Chris

WSU

On Nov 20, 2008, at 9:34 AM, Jerome Henin wrote:

> Hi Chris,
>
> On Thu, Nov 20, 2008 at 12:04 PM, Christopher Hartshorn
> <cmhartshorn_at_wsu.edu> wrote:
>> Hi Jerome,
>>
>> First off, I want to tell you how much I appreciate your response.
>> I read
>> the publication you recommended as well as two referenced works, your
>> BiophysJ pub. and the Free Energy Calculations reference text. All
>> good
>> reads. Although, I still am not understanding two aspects of the FEP
>> protocol that is done in that double annihilation method in the
>> publication
>> by Christophe.
>> First, am I correct in thinking that there are a total of two FEP's
>> performed on the same initial trajectory (at the 31ns point) and
>> that each
>> of these FEP's are performed for 12.1 ns?
>
> Almost. One of the transformations involves the ligand bound to the
> receptor: it starts from the 31ns point. The other one, just the
> ligand in water, starts from some random initial configuration; the
> conformational sampling problem in not that acute in this second case
> anyway. The second calculation involves a much smaller system, so it's
> also much cheaper.
>
>> Next, I am not sure what is being turned on/off with respect to
>> what else
>> (e.g. What has its beta column as 1,0, or -1?)
>
> The ligand is being turned off, i.e. has -1 flags, in both
> transformations. That's all.
>
>> Finally, how do I get the developers copy of NAMD? I would like to
>> try this
>> as well.
>
> The instructions are there, under "bleeding edge":
> http://www.ks.uiuc.edu/Research/namd/development.html
> You'll need to download and compile Charm++ first. In simple cases,
> that can be as easy as untarring and typing "./build charm++
> net-linux".
>
> The document below takes you through a typical process of building
> namd:
> http://www.ks.uiuc.edu/Research/namd/2.6/notes.html#compiling
>
> Best,
> Jerome

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