Analytical Continuum Solvent (ACS) Potential
Purpose: calculate solvation free energy and forces based on
a continuum description of the solvent, in particular the analytical
continuum electrostatics (ACE) potential.
Please report problems to Michael Schaefer at schaefer@brel.u-strasbg.fr
WARNING: The module is still being developed and may change in future versions.
SERIOUS WARNING: The use of ACE in MD calculations may do harm to your protein
and actually unfold it. DO NOT EXPECT THE POTENTIAL TO BE VIABLE FOR PROTEIN
FOLDING CALCULATIONS, even though it has been successfully used for peptides
with less than 15 residues.
REFERENCES:
M. Schaefer & M. Karplus (1996) J. Phys. Chem. 100, 1578-1599.
M. Schaefer, C. Bartels & M. Karplus (1998) J. Mol. Biol., in press.
* Menu:
* Syntax:: Syntax of the ACE specifications
* Defaults:: Defaults and Recommended values
* Function:: Purpose of each of the specifications
* Examples:: Usage examples of the ACE module
Syntax
[SYNTAX ACE functions]
Syntax: The ACE specifications can be specified any time the nbond
specification parser is invoked, e.g.,
ENERgy [other-spec] [ace-spec]
ace-spec::=
[ ACE ] [ IEPS real ] [ SEPS real ] [ ALPHa real ] [ SIGMa real ]
The defaults for the ACE potential are IEPS 1.0 SEPS 80.0 ALPHa 1.2 SIGMa 3.0 In the current implementation, ACE should be used with united atom parameters, ALPHa set equal to 1.2 and the PARAM19 parameter file param19-1.2.inp; the param19-1.2.inp file (in the ./test/data/ subdirectory) inludes a table of atom volumes at the end which is compatible with ALPHa 1.2.
0. Introduction
The analytical continuum solvent (ACS) potential is introduced to
perform molecular dynamics/minimization calculations with a continuum
approximation of the solvent.
Two solvent contributions to the effective (free) energy of a solute
are included: the electrostatic solvation free energy, and the
non-polar (i.e., non-electrostatic) solvation free energy.
The first (electrostatic) contribution (G_el) is calculated using an
analytical approximation to the solution of the Poisson-equation
called ACE (from: analytical continuum electrostatics).
The non-polar solvation free energy (G_np) is approximated by a pairwise
potential which yields results that are very similar to the well-known
surface area approximations of the hydrophobic (solvation) energy
(e.g., Wesson and Eisenberg, Prot. Sci. 1 (1992), 227--235; see
the ASP potential in CHARMM).
Restriction:
The ACE solvation potential has to be used together with no cutoff or with
atom based switching.
Compatibility:
1. ACE can be used with BLOCK (but: the diagonal elements of the BLOCK
matrix MUST NOT be zero).
2. ACE can be used with fixing atoms (CONS FIX); the resulting energy and
forces are an approximation, because all the interaction-dielectric terms
of the potential (eq (47) in Schaefer & Karplus, JPC 100 (1996), 1578)
which involve two fixed atoms are neglected, despite the fact that they
exist and that they are NOT invariant!
Meaning of the ACE parameters:
1. IEPS
Dielectric constant for the space occupied by the atoms that are treated
explicitly, e.g., the space occupied by the protein.
2. SEPS
Dielectric constant for the space occupied by the solvent that is treated
as a continuum (i.e., the complement of the space occupied by the protein).
3. ALPHa
The volumes occupied by individual (protein) atoms are described by
Gaussian density distributions. The factor ALPHa controls the width of these
Gaussians. The net volume of the individual atom Gaussian distributions is
defined in the volume table at the end of the parameter file param19-1.2.inp.
The width of the atom volume distributions and the volume table have to
be consistent -- currently, the volumes in the param19-1.2.inp file are
optimal for an ALPHa of 1.2. Changing ALPHa without adapting the volume
table is expected to reduce the precision of the results.
4. SIGMa
The ACE solvation potential includes a hydrophobic contribution
which is roughly proportional to the solvent accessible surface area.
The factor SIGMa scales the hydrophobic contribution. For peptides
with about 10-15 residues, a SIGMa factor of 3 results in hydrophobic
contributions that are approximately equal to the solvent accessible
surface area multiplied by 8 cal/(mol*A*A).
Examples
To set up simulations/minimizations with the ACE solvation potential,
the following energy call is expected to be adequate in most situations:
ENERgy ATOM ACE IEPS 1.0 SEPS 80.0 ALPHa 1.2 SIGMa 3 SWITch -
VDIS VSWI CUTNB 13.0 CTONNB 8.0 CTOFNB 12.0
When you run molecular dynamics or minimization with ACE, you get
two more lines in the log file printout with energy terms, e.g.,
DYNA DYN: Step Time TOTEner TOTKe ENERgy TEMPerature
DYNA PROP: GRMS HFCTote HFCKe EHFCor VIRKe
DYNA INTERN: BONDs ANGLes UREY-b DIHEdrals IMPRopers
DYNA EXTERN: VDWaals ELEC HBONds ASP USER
DYNA PRESS: VIRE VIRI PRESSE PRESSI VOLUme
DYNA ACE1: HYDRophobic SELF SCREENing COULomb
DYNA ACE2: SOLVation INTERaction
---------- --------- --------- --------- --------- ---------
DYNA> 0 0.00000 -3423.29671 0.00000 -3423.29671 0.00000
DYNA PROP> 4.45310 -3423.12228 0.52327 0.17442 -532.70519
DYNA INTERN> 6.58717 60.43092 0.00000 56.00750 7.32144
DYNA EXTERN> -380.26218 -3173.38156 0.00000 0.00000 0.00000
DYNA PRESS> 0.00000 355.13679 0.00000 0.00000 0.00000
DYNA ACE1> 109.04469 -3829.20991 2750.59427 -2203.81062
DYNA ACE2> -1078.61564 546.78365
---------- --------- --------- --------- --------- ---------
and the same during minimization (MINI...) or after
an energy calculation (ENER...).
The terms in lines with ACE1 and ACE2 are:
HYDRophobic: Hydrophobic potential, equivalent to a surface based
solvation term proportional to the sigma input parameter;
SELF: Self contribution to electrostatic solvation free energy,
Delta-E_self, first term of eq(8) (i.e., sum over all atomic
solvation energies, Delta-E_self_i, eq(28));
SCREENing: Interaction contribution to electrostatic solvation free energy,
i.e., screening of Coulomb interactions, eq(38) (sum over all
atom pairs, including bonded and 1-3 atom pairs!);
COULomb: Coulomb energy with constant dielectric of EPSI (sum over
all atom pairs for the first term in eq(36) -- excluding
bonded and 1-3 atom pairs, and 1-4 atom pair contributions
scaled with E14FAC);
SOLVation: Electrostatic (!) solvation free energy, sum of SELF and
SCREENing;
INTERaction: Electrostatic interaction, sum of SCREENing and COULomb
(eq(36), but taking account of the bonded, 1-3, and 1-4
exclusion in the Coulomb term, see above).
The term "ELEC" in line "DYNA EXTERN>..." is the total electrostatic energy:
ELEC: Sum of SELF, SCREENing, COULomb.
Equation numbers refer to Schaefer & Karplus, J. Phys. Chem. 100 (1996), 1578.
see also: test cases c26test/ace1.inp and c26test/ace2.inp.
NIH/DCRT/Laboratory for Structural Biology
FDA/CBER/OVRR Biophysics Laboratory
Modified, updated and generalized by C.L. Brooks, III
The Scripps Research Institute