Subject: trajectory: summary

From: Rino Ragno <[email-masked]>
Date: Fri, 10 Apr 1998 17:07:08 -0500 (CDT)

Hi,

few days ago I posted the following:

>Given the initial(A) and final(B) geometry of two conformation of a protein
>how can I generate the trajectory of the interconversion A <-> B and store
>the intermediate files, say for istance 20 conformation?

>Is any of you out there aware of a program that solve the above problem.

Next are the answers I got.

1 ===================================================

The simplest is to run an MD trajectory with distance (and maybe other)
constraints
starting with your initial conformation while constraints are extracted
>from your final conformation

any MD program such as CHARMM or Discover or other

Philippe

2  ===================================================

From: Michael Hodgson <[email-masked]>

Well I've never tried anything like this, but I believe it might be
possible using travel, under CHARMM.  I've never read the documentation
but it is available on the web at:

http://yuri.harvard.edu/charmm/travel.html

-Michael

3  ===================================================

From: Richard Gillilan <[email-masked]>

Obtaining actual trajectories connecting initial and final conformations
is a problem in variational calculus (of great interest in Semiclassical
calculations and other areas). I have a paper in JCP some years
ago that describes what I call the "Variational Verlet" method, which is
quite simple in concept but leads to equations that are difficult to
solve globally. The problem is that trajectories of any significant
length are generally saddle points in the multidimensional space of
of possible solutions rather than minima or maxima. This is a fundamental
problem that you will encounter with any such calculation that gives a true
trajectory. Back when I did my calculations in 1992, I worked with only
about 100 atoms and finding convergent solutions was difficult but not
impossible. The theory does have some very interesting properties: there
is formally NO accumulation of integration error with time (sounds impossible
doesn't it? One pays for it in other ways I suspect). Bill Hoover at Livermore
has introduced Lagrange multipliers into the equations to obtain true
nonequilibrium const Temp trajectories. Here are the papers:

"Shadowing, rare events and rubber bands. A variational Verlet algorithm
for molecular dynamics", Richard E. Gillilan and Kent R. Wilson
J. Chem Phys. 97 (3) 1 Aug 1992

William Hoover Phys Lett A vol 204 p133 (1995)

Sorry, the code was rather specialized and not designed for biomolecules,
perhaps someday I'll integrate it with my simulation suite
that uses MMFF94.

If you don't need true trajectories, I suggest you look at Ron Elber's
work on reaction path calculations. His code is publically available
and works with proteins:

R. Czerminski and R. Elber, Int. J. Quant. Chem. 24, 167 (1990)

4  ===================================================

From: Rick Venable <[email-masked]>

I know CHARMM can be used to do such things, and I suspect AMBER,
DISCOVER, and GROMOS can as well.  None are free, but all but DISCOVER are
available to academic sites for a few hundred dollars from research groups
at the originating university.

However, depending on the number of degrees of freedom involved in going
>from state A to state B, there may be more than one pathway.

5  ===================================================

From: Ferenc Molnar <[email-masked]>
Dear Rino:

take a look at:

J. Schlitter, M. Engels, P. Kr\"uger, E. Jacoby, A. Wollmer,
"Targeted Molecular Dynamics Simulation of Conformational
Change - Application to the T <-> R Transition in Insulin",
Molecular Simulation, _10_, 291-308 (1993).

J. Ma, M. Karplus,
"Molecular switch in signal transduction: Reaction path of
the conformational changes in ras p21",
Proc.Natl.Acad.Sci. USA, _94_, 11905-11910 (1997).

Cheers,

Ferenc

6  ===================================================

From: [email-masked]

 Rino,

     You need one of the reaction path methods of Ron Elber, et al. The
 simplest of his methods is implemented in TINKER as the "path" tool. It
 works well on small molecules through medium-sized peptides, and might
 be pushed to do some small protein problems. Some of Elber's more
 sophisticated versions can certainly do big protein problems. All of
 these Elber methods do exactly what you asked for -- they take two
 endpoint structures as input and generate a series of structures on
 the conformational path connecting them.

                                  Jay

7  ===================================================

From: "Adrian Roitberg" <[email-masked]>

Unfortunately, not what you ask for is not trivial.
You should look at Ron Elber's work over the last 8-9 years for a reaction path
between those conformations, and to his recent work ('97" for actual
trajectories.

8  ===================================================

From: Ryszard Czerminski <[email-masked]>

Hi Rino,

Check

(1) http://www.fh.huji.ac.il/members/Elber/index.html
    and program Moil

(2) http://dasher.wustl.edu/tinker

Moil and Tinker have implementation of some of the aproaches
published in

@ARTICLE{Elber87,
  author = "Ron Elber and Martin Karplus",
  title = {},
  journal = CPL, year = 1987, volume = 139, pages = "375" }

\item {11.}{R. Czermi\'nski, R. Elber
"Reaction Path Study of Conformational
Transitions and Helix Formation in a Tetrapeptide"
Proc. Nat. Acad. Sci. 86, 6963 (1989)

\item {12.}{R. Czermi\'nski, R. Elber
"Reaction Path Study of Conformational
Transitions in Flexible Systems: Applications to Peptides"
J. Chem. Phys. 92, 5580 (1990)

\item {17.}{R. Czermi\'nski, R. Elber
"Self Avoiding Walk Between Two Fixed Points as a Tool to Calculate
Reaction Paths in Large Molecular Systems"
Int. J. Quant. Chem. 24, 167 (1990)

R. Olender and Ron Elber, "Caclulation of classical trajectories with a
very large time step: Formalism and numerical examples",
J. Chem. Phys. 105,9299-9315(1996)

(3) http://yuri.harvard.edu (CHARMM HomePage)

    It has implementation of PATH and TRAVEL (developed by Stefan Fisher)

@ARTICLE{FisherKarplus92,
  author = "S. Fisher and M.Karplus",
  title = {},
  journal = CPL, year = 1992, volume = "194", pages = "252" }

@PHDTHESIS{Fisher92,
  author = "S. Fisher",
  title  = {Curvilinear reaction-coordinates of conformational change
            in macromolecules. Application to rotamase catalysis},
  school = {Harvard University},
  year   = 1992,
  address = {Cambridge, MA} }

9  ===================================================

From: Devapriya Choudhury <[email-masked]>

Hello,
  I guess one should do energy minimisation where the RMS diff. between A
and B is added to the potential energy (after suitable weighting).
However, I don't know whether there are any programs to do this, or even
if there is any better way to do this.
  Please post me any replies you get on this issue.

cheers
Deva

10  ===================================================

From: [email-masked]

Juergen Schlitter devised an algorithm called targeted molecular dynamics
(TMD), which you'll find described in

Schlitter J, Engels M, Kruger P: J Mol Graph 1994 Jun;12(2):84-89
"Targeted molecular dynamics: a new approach for searching pathways of
conformational transitions."

J. Schlitters web page can be found at
	http://www.bph.ruhr-uni-bochum.de/~juergen/

Hope this helps,

	Lutz

11 ===================================================

From: Andrew Dalke <[email-masked]>

Hello,

  I wrote a simple linear interpolation script for the program
VMD.  The example and tutorial is at
   http://www.ks.uiuc.edu/Research/vmd/mailing_list/

Once it is generated you can animate it, save it, etc.  VMD
is available for several version of unix.

  For every program there will be a problem of how to define
the transformation that takes you from one set of coordinates
to the other in a physically realistic manner.  I don't think
there is any program that can do that -- or we would have
the protein folding problem solved :)

12  ===================================================

From: "Jeffrey L. Nauss" <[email-masked]>

This exactly what CHARMm will do using the TRAVEL routine.  Look at either
the MSI or Harvard WWW site for documentation.  If you have difficulty
finding anything about TRAVEL, please let me know.  I'll go through my
sources when I return to my office on Thursday or Friday.

===================================================
===================================================

Thanks a lot to all

Rino

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