AMBER Archive (2008)

Subject: Re: AMBER: SMD-related questions

From: M. L. Dodson (
Date: Mon Dec 29 2008 - 12:25:19 CST

Alessandro Nascimento wrote:
> Hi guys,
> I have been through the manual but could not find the units of force
> for SMD. I assume it is pN as in NAMD. Is that correct?

I have not done the dimensional analysis, but that does not sound
right (unless the units just conspire to work out that way). Others
should correct me if I am wrong.

> A second question is: the steering velocity is not set, as in NAMD, in
> the simulation input file. I presume it is given by the steering
> distance over the simulation time (r2a/nstlim). Is that correct?

I believe that is correct.

> Could someone also provide some references (or share personal
> experiences) regarding the spring constant on SMD simulations
> (especially in Amber FF)?
> Thanks a lot in advance and a happy new year for all,
> --alessandro

Here are a few references to keep you off the streets. One of them
(at least) should address your question. In particular, look at the
Park et al., J. Chem. Phys. and the Balsera et al., Biophys. J.
papers. (My answer: The spring constant should be sufficiently large
that movement along the steered coordinate is relatively smooth, the
targeted and actually achieved distances should be close to each other
and you should run enough replicates to remove the influence of the
spring constant when you Jarzynski average. In any case, you asked
what people do, and those are things I consider. Others may chime in
to tell me I am wrong, etc.)

        abstract = {There are only a very few known relations in
        statistical dynamics that are valid for systems driven
        arbitrarily far-from-equilibrium. One of these is the
        fluctuation theorem, which places conditions on the entropy
        production probability distribution of nonequilibrium
        systems. Another recently discovered far from equilibrium
        expression relates nonequilibrium measurements of the work
        done on a system to equilibrium free energy differences. In
        this paper, we derive a generalized version of the fluctuation
        theorem for stochastic, microscopically reversible
        dynamics. Invoking this generalized theorem provides a
        succinct proof of the nonequilibrium work relation.},
        address = {Department of Chemistry, University of California
        at Berkeley, Berkeley, California 94720,
        author = {Crooks, G. E. },
        citeulike-article-id = {460558},
        issn = {1063-651X},
        journal = {Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics},
        keywords = {non-equiriblium},
        month = {September},
        number = {3},
        pages = {2721--2726},
        posted-at = {2006-01-17 07:37:58},
        priority = {2},
        title = {Entropy production fluctuation theorem and the
        nonequilibrium work relation for free energy differences.},
        url = {},
        volume = {60},
        year = {1999}

   author = {{Ytreberg}, F.~M.},
    title = "{Absolute FKBP binding affinities obtained via
    non-equilibrium unbinding simulations}",
  journal = {ArXiv e-prints},
archivePrefix = "arXiv",
   eprint = {0710.5132},
 keywords = {Physics - Biological Physics, Physics - Computational Physics},
     year = 2007,
    month = oct,
   adsurl = {},
  adsnote = {Provided by the SAO/NASA Astrophysics Data System}

  author = {C. Bustamante and J. Liphardt and F. Ritort},
  title = {The nonequilibrium thermodynamics of small systems},
  journal = {PHYSICS TODAY},
  volume = {58},
  pages = {43},
  url = {},
  year = {2005}

  title = {Equilibrium free-energy differences from nonequilibrium
  measurements: A master-equation approach},
  author = {Jarzynski, C. },
  journal = {Phys. Rev. E},
  volume = {56},
  number = {5},
  pages = {5018--5035},
  numpages = {17},
  year = {1997},
  month = {Nov},
  doi = {10.1103/PhysRevE.56.5018},
  publisher = {American Physical Society}
author = {David D. L. Minh and Artur B. Adib},
collaboration = {},
title = {Optimized free energies from bidirectional single-molecule
force spectroscopy},
publisher = {APS},
year = {2008},
journal = {Physical Review Letters},
volume = {100},
number = {18},
eid = {180602},
numpages = {4},
pages = {180602},
url = {},
doi = {10.1103/PhysRevLett.100.180602}

%% Journal of Molecular Graphics and Modelling, Volume 19, Issue 1,
%% February 2001, Pages 13-25
%% Barry Isralewitz, Jerome Baudry, Justin Gullingsrud, Dorina Kosztin
%% and Klaus Schulten
@article {Isralewitz:SMD,
        author = "Isralewitz B.",
        author = "Baudry J.",
        author = "Gullingsrud J.",
        author = "Kosztin D.",
        author = "Schulten K.",
        title = "Steered molecular dynamics investigations of protein function",
        journal = "Journal of Molecular Graphics and Modelling",
        volume = "19",
        year = "February 2001",
        abstract = "",
        pages = "13-25(13)",
        url =
        doi = "doi:10.1016/S1093-3263(00)00133-9"

author = {Paul Maragakis and Martin Spichty and Martin Karplus},
collaboration = {},
title = {Optimal estimates of free energies from multistate nonequilibrium work data},
publisher = {APS},
year = {2006},
journal = {Physical Review Letters},
volume = {96},
number = {10},
eid = {100602},
numpages = {4},
pages = {100602},
keywords = {free energy; thermodynamics; chemical reactions},
url = {},
doi = {10.1103/PhysRevLett.96.100602}

author = {David D. L. Minh},
collaboration = {},
title = {Free-energy reconstruction from experiments performed under
different biasing programs},
publisher = {APS},
year = {2006},
journal = {Physical Review E (Statistical, Nonlinear, and Soft Matter Physics)},
volume = {74},
number = {6},
eid = {061120},
numpages = {4},
pages = {061120},
keywords = {free energy; nonequilibrium thermodynamics; protocols;
fluctuations; statistical analysis},
url = {},
doi = {10.1103/PhysRevE.74.061120}

author = {Jarzynski, C.},
title={{How does a system respond when driven away from thermal equilibrium?}},
journal = {Proceedings of the National Academy of Sciences of the
United States of America},
volume = {98},
number = {7},
pages = {3636-3638},
doi = {10.1073/pnas.081074598},
year = {2001},
URL = {},
eprint = {}

author = {Hummer, Gerhard and Szabo, Attila},
title={{Free energy reconstruction from nonequilibrium single-molecule
pulling experiments}},
journal = {Proceedings of the National Academy of Sciences of the
United States of America},
volume = {98},
number = {7},
pages = {3658-3661},
doi = {10.1073/pnas.071034098},
year = {2001},
abstract = {Laser tweezers and atomic force microscopes are
increasingly used to probe the interactions and mechanical properties
of individual molecules. Unfortunately, using such time-dependent
perturbations to force rare molecular events also drives the system
away from equilibrium. Nevertheless, we show how equilibrium free
energy profiles can be extracted rigorously from repeated
nonequilibrium force measurements on the basis of an extension of
Jarzynski's remarkable identity between free energies and the
irreversible work.},
URL = {},
eprint = {}

author = {Gore, Jeff and Ritort, Felix and Bustamante, Carlos},
title={{Bias and error in estimates of equilibrium free-energy
differences from nonequilibrium measurements}},
journal = {Proceedings of the National Academy of Sciences of the
United States of America},
volume = {100},
number = {22},
pages = {12564-12569},
doi = {10.1073/pnas.1635159100},
year = {2003},
URL = {},
eprint = {}

   author = {{Park}, S. and {Khalili-Araghi}, F. and {Tajkhorshid}, E. and
        {Schulten}, K.},
    title = "{Free energy calculation from steered molecular dynamics
    simulations using Jarzynski's equality}",
  journal = {Journal Chemical Physics},
 keywords = {molecular dynamics method, molecular biophysics, organic compounds},
     year = 2003,
    month = aug,
   volume = 119,
    pages = {3559-3566},
      doi = {10.1063/1.1590311},
   adsurl = {},
  adsnote = {Provided by the SAO/NASA Astrophysics Data System}

author = {Balsera, M and Stepaniants, S and Izrailev, S and Oono, Y and Schulten, K},
title = {{Reconstructing potential energy functions from simulated
force-induced unbinding processes.}},
journal = {Biophys. J.},
volume = {73},
number = {3},
pages = {1281-1287},
year = {1997},
abstract = {One-dimensional stochastic models demonstrate that
molecular dynamics simulations of a few nanoseconds can be used to
reconstruct the essential features of the binding potential of
macromolecules. This can be accomplished by inducing the unbinding
with the help of external forces applied to the molecules, and
discounting the irreversible work performed on the system by these
forces. The fluctuation-dissipation theorem sets a fundamental limit
on the precision with which the binding potential can be reconstructed
by this method. The uncertainty in the resulting potential is linearly
proportional to the irreversible component of work performed on the
system during the simulation. These results provide an a priori
estimate of the energy barriers observable in molecular dynamics
URL = {},
eprint = {}

M. L. Dodson
Business Email: activesitedynamics-at-comcast-dot-net
Personal Email:	mldodson-at-comcast-dot-net
Phone:	eight_three_two-56_three-386_one
The AMBER Mail Reflector
To post, send mail to
To unsubscribe, send "unsubscribe amber" (in the *body* of the email)