Effective Energy Function 1
EEF1 is an effective energy function combining the CHARMM 19 polar
hydrogen energy function (with certain modifications, see below)
with an excluded volume implicit solvation model. The solvation model
is similar in spirit to the Atomic Solvation Parameter approach, but
does not use surface areas and is therefore much faster. Latest
benchmarks say that simulations with EEF1 take about 50% longer
than the corresponding vacuum simulation.
The solvation model assumes that the solvation free energy of each
group is equal to the solvation free energy of that group in a small
model compound less the amount of solvation it loses due to solvent
exclusion by other atoms of the macromolecule around it. The exclusion
effect of nearest and next-nearest neighbors (1-2 and 1-3 interactions)
are neglected because such neighbors also exist in small model compounds.
The CHARMM nonbonded atom and exlusion lists are used for the solvation
calculation.
Because not only DG but also DH and DCp data are available, we
can calculate the solvation free energy at different temperatures.
This calculation assumes a DCp independent of temperature.
Therefore extrapolation to temperatures very different from 300 K
is not reliable.
EEF1 refers not only to the implicit solvation model but also to
the specific modifications and nonbonded options used in CHARMM.
The nonbonded options must be: ctonnb 7. ctofnb 9. cutnb 10. group rdie
(see example file below).
Three files are needed to use EEF1:
toph19_eef1.inp : This is a modification of toph19.inp where ionic
sidechains and termini are neutralized and contains
an extra parameter type (CR)
param19_eef1.inp: This is a modification of param19.inp which includes
the extra parameter type (CR)
solvpar.inp : This file contains the solvation parameters
When the INTE command is used with EEF1, the number listed under
ASP is the amount of solvation free energy that is excluded between the
two atom selections. For example, the INTE between atom A and atom B will
give the amount of solvation A loses due to B plus the amount B loses due
to A. The command "INTE sele all end" will give the amount of solvation free
energy excluded, not the total solvation free energy of all atoms. That
is, it is not equivalent to "ENERGY".
EEF1 can be used with images. In that case the ASP energy term
refers to the solvation free energy of the primary atoms. This is usually
less negative than when images are not present, because image atoms exclude
some solvation free energy from the primary atoms.
EEF1 is compatible with the BYCC non-bonded option and the NBACtive
command, so that the calculation of non-bonded and solvation energy terms
can be limited to specific subsets of atoms in the system.
* Menu:
* Syntax:: Syntax of the EEF1 commands
* References:: Useful references
* Example:: Input file
Syntax for EEF1
There are only two EEF1 commands:
EEF1 SETUP [TEMP real] UNIT int NAME solv_param_file
EEF1 PRINT
The first sets up the solvation calculation by giving TEMP
and reading in the solvation parameters. And the second
prints out the solvation of each group. The solvation energy
is stored in ETERM(ASP) and reported under the name "ASP".
Obviously, it makes no sense to use both ASP and EEF1.
If one wants to skip the solvation term after one has set it
up, one can issue the command SKIP ASP.
TEMP is the temperature to which the solvation parameters refer to
(default is 298.15). Note that this is unrelated to the
temperature at which one runs dynamics. It just determines
the solvation free energy parameter values.
PRINT prints out the solvation free energy of each atom/group
as well as the solvation enthalpy and heat capacity
References
[1] T. Lazaridis and M. Karplus, Effective energy function for
proteins in solution, Proteins, 35:133-152 (1999)
[2] T. Lazaridis and M. Karplus, Discrimination of the native from
misfolded protein models with an energy function including
implicit solvation, J. Mol. Biol., 288:477-487 (1999)
[3] T. Lazaridis and M. Karplus, "New View of Protein Folding
reconciled with the Old through Multiple Unfolding Simulations",
Science, 278:1928 (1997)
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* Example file for EEF1
*
open read card unit 3 name toph19_eef1.inp
read rtf unit 3 card
close unit 3
open read card unit 3 name param19_eef1.inp
read para unit 3 card
close unit 3
open read unit 3 card name filename.crd
read seque coor unit 3
close unit 3
generate main setup
open read unit 2 card name filename.crd
read coor card unit 2
close unit 2
! IMPLICIT SOLVATION SETUP COMMAND
! The nonbonded options below are part of the model
eef1 setup temp 298.15 unit 93 name solvpar.inp
update ctonnb 7. ctofnb 9. cutnb 10. group rdie
mini abnr nstep 300
!This command prints out solvation free energy for each atom
eef1 print
dynamics verlet timestep 0.002 nstep 1000 nprint 100 iprfrq 100 -
firstt 240 finalt 300 twindh 10.0 ieqfrq 200 ichecw 1 -
iasors 0 iasvel 1 inbfrq 20
inte sele resid 2 end sele resid 19 end
!the command below is not equivalent to energy
inte sele all end
energy
skip asp
energy
stop
NIH/DCRT/Laboratory for Structural Biology
FDA/CBER/OVRR Biophysics Laboratory
Modified, updated and generalized by C.L. Brooks, III
The Scripps Research Institute