- Contemporary messages sorted: [ by date ] [ by thread ] [ by subject ] [ by author ] [ by messages with attachments ]

From: Jason Swails <jason.swails.gmail.com>

Date: Tue, 17 Jul 2012 08:58:46 -0400

They are two completely different methods for calculating vibrational

entropies. One relies more or less on PCA vectors to describe vibrations

(with the corresponding eigenvalues as the vibrational frequencies). The

other relies on a normal mode approximation whereby the Hessian is

diagonalized to obtain frequencies.

To illustrate how these methods could give drastically different entropies,

imagine a large free energy well whose fine-grained structure has many

local minima (the best example I could find in 3 seconds is here:

http://ej.iop.org/images/1478-3975/8/3/035003/Full/pb373205fig03.jpg). As

long as the barriers between the minima are relatively low, you will get

vibrational frequencies that look like they come from the vibrational

frequencies derived from the large, single free energy well. Nmode

entropies, on the other hand, will appear as though they come directly from

whatever local free energy minimum they were minimized to (so a local

minima, rather than the global well). I think these would give quite

different answers, and would help explain why quasi-harmonic calculations

take so many frames to converge.

Also, the solvation method you used for the normal mode analysis is almost

certainly different than what you used to propagate the dynamics. Ergo,

even if your system stayed in the same free energy well in a single

simulation, the shape of that well would be different between vacuum/igb=1

(the only two options for nmode) and that of the original simulation

(likely explicit solvent). As a result, you should expect different

answers.

If you want to get the *same* answers, run a simulation in implicit solvent

(igb=1) at very low temperatures (20-50K), and do your quasi-harmonic calc

with those frames. The low temperature should force you to stay in a

single well. Then, perform a normal mode calculation on a minimized

structure (making sure to adjust the temperature in both the ptraj code and

nab/sff code to get the right values, or calculate the entropy of each mode

by hand given the frequencies). I think I recall a colleague of mine

running this exact test and finding they converged to the same answer (but

it was a long time ago and the details are long buried :))

HTH,

Jason

On Tue, Jul 17, 2012 at 7:38 AM, George Tzotzos <gtzotzos.me.com> wrote:

*> I would be grateful if anyone could provide an explanation regarding the
*

*> huge differences in total Delta S given by the two methods.
*

*>
*

*> Below are the results obtained for exactly the same trajectories
*

*>
*

*> Solvated complex topology file: 2wc6_bom_solv.prmtop
*

*> |Complex topology file: 2wc6_bom.prmtop
*

*> |Receptor topology file: 2wc6.prmtop
*

*> |Ligand topology file: bom.prmtop
*

*> |Initial mdcrd(s): prod_10ns.mdcrd
*

*> | prod_2ns.mdcrd
*

*> | prod_4ns.mdcrd
*

*> | prod_6ns.mdcrd
*

*> | prod_8ns.mdcrd
*

*> |
*

*> |Best guess for receptor mask: ":1-141"
*

*> |Best guess for ligand mask: ":142"
*

*> |Ligand residue name is "BOM"
*

*> |
*

*> |Calculations performed using 1000 frames.
*

*> |NMODE calculations performed using 20 frames.
*

*>
*

*> DELTA S total= -21.7086 +/- 1.5570
*

*>
*

*> ENTROPY RESULTS (QUASI-HARMONIC APPROXIMATION) CALCULATED WITH PTRAJ:
*

*>
*

*> DELTA S: -12.5924 -10.2513 -56.3566 -79.2006
*

*>
*

*>
*

*> Many thanks in advance
*

*>
*

*> George
*

*>
*

*>
*

*> _______________________________________________
*

*> AMBER mailing list
*

*> AMBER.ambermd.org
*

*> http://lists.ambermd.org/mailman/listinfo/amber
*

*>
*

Date: Tue, 17 Jul 2012 08:58:46 -0400

They are two completely different methods for calculating vibrational

entropies. One relies more or less on PCA vectors to describe vibrations

(with the corresponding eigenvalues as the vibrational frequencies). The

other relies on a normal mode approximation whereby the Hessian is

diagonalized to obtain frequencies.

To illustrate how these methods could give drastically different entropies,

imagine a large free energy well whose fine-grained structure has many

local minima (the best example I could find in 3 seconds is here:

http://ej.iop.org/images/1478-3975/8/3/035003/Full/pb373205fig03.jpg). As

long as the barriers between the minima are relatively low, you will get

vibrational frequencies that look like they come from the vibrational

frequencies derived from the large, single free energy well. Nmode

entropies, on the other hand, will appear as though they come directly from

whatever local free energy minimum they were minimized to (so a local

minima, rather than the global well). I think these would give quite

different answers, and would help explain why quasi-harmonic calculations

take so many frames to converge.

Also, the solvation method you used for the normal mode analysis is almost

certainly different than what you used to propagate the dynamics. Ergo,

even if your system stayed in the same free energy well in a single

simulation, the shape of that well would be different between vacuum/igb=1

(the only two options for nmode) and that of the original simulation

(likely explicit solvent). As a result, you should expect different

answers.

If you want to get the *same* answers, run a simulation in implicit solvent

(igb=1) at very low temperatures (20-50K), and do your quasi-harmonic calc

with those frames. The low temperature should force you to stay in a

single well. Then, perform a normal mode calculation on a minimized

structure (making sure to adjust the temperature in both the ptraj code and

nab/sff code to get the right values, or calculate the entropy of each mode

by hand given the frequencies). I think I recall a colleague of mine

running this exact test and finding they converged to the same answer (but

it was a long time ago and the details are long buried :))

HTH,

Jason

On Tue, Jul 17, 2012 at 7:38 AM, George Tzotzos <gtzotzos.me.com> wrote:

-- Jason M. Swails Quantum Theory Project, University of Florida Ph.D. Candidate 352-392-4032 _______________________________________________ AMBER mailing list AMBER.ambermd.org http://lists.ambermd.org/mailman/listinfo/amberReceived on Tue Jul 17 2012 - 06:00:02 PDT

Custom Search