Re: [AMBER] problems with relative TI calculations

From: <>
Date: Thu, 18 Jun 2015 16:18:34 +0000

I explicitly set noshakemask to the organic molecule (and dt=0.001), so no.

Many thanks,

From: Brian Radak []
Sent: 18 June 2015 17:01
To: AMBER Mailing List
Subject: Re: [AMBER] problems with relative TI calculations

Just a wild guess - Are you using SHAKE? Is there a problem mapping a C-H
bond to a C-C bond in the transformation?


On Thu, Jun 18, 2015 at 4:35 AM, <> wrote:

> Hi,
> I have run into some problems with relative TI calculations. I am
> interested in testing the relative hydration free energy of a set of small
> organic molecules. What I find is that the default 1-step protocol
> (simultaneous LJ and electrostatic softcores) in sander and pmemd does not
> work in some cases. One of them is neopentane > methane. The methane is
> mapped such that its carbon overlaps with the central C of neopentane. The
> 12 hydrogens of neopentane are defined as softcore atoms.
> The 1-step protocol suggest a relative free energy of about 7 kcal/mol
> which is clearly too much as experiment suggests a value around 0
> kcal/mol. To further test this I have run "absolute" TI simulations, a
> 3-step (complete decharging, vdw+bondend and recharging transformation; the
> latter is zero for methane in both solution and vacuum) and a 2-step
> protocol (the intermediate state is a neopentane with methane charges, the
> softcores have zero end-charges; the second step is a vdw+bonded
> transformation of this intermediate to the final state). All of these give
> me a free energy close to 0 kcal/mol so quite different from the 1-step
> protocol. An alternative mapping (methane C to terminal C in neopentane)
> gives me 1.2 kcal/mol in the 1-step protocol and kcal/mol in the 3-step
> protocol,.
> I have also noticed in the neopentane > methane mutation that the final
> C-H distance of the methane end state is 1.22 Angstrom instead of the
> expected 1.09 A. This is regardless of chosen protocol. So I have also
> tested this with tert-butane and propane (methane again mapped to central
> carbon) to find end-point distances of 1.18 A and 1.14 A in vacuo.
> I do not know what is going on here but some things clearly don't match up.
> Many thanks,
> Hannes.
> _______________________________________________
> AMBER mailing list

Brian Radak
Postdoctoral Scholar
University of Chicago
Department of Biochemistry & Molecular Biology
Gordon Center for Integrative Science, W323A
929 E. 57th St.
Chicago, IL 60637-1454
Tel: 773/834-2812
AMBER mailing list
AMBER mailing list
Received on Thu Jun 18 2015 - 09:30:04 PDT
Custom Search