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.

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