Subject: Improper dihedrals in GROMOS

From: "G. Ravishanker" <[email-masked]>
Date: Tue, 23 Nov 1993 08:37:35 -0500

This is a question regarding the improper dihedral parameters for the side
chains of two amino acids, VAL and LEU, as it appears in the GROMOS
parameter files. The residue topology file lists an entry for the
following improper dihedral angles:

	VAL: CB CG1 CG2 CA
	LEU: CG CD1 CD2 CB

The force constants for both these are 80 kcal/mol-1/rad-2 and the
equilibrium angle is 35.264.  In VAL, CG1 and CG2, and in LEU, CD1 and CD2
are identical united atom CH3's. However, it is clear that the improper
dihedral angle measured depends on the order of the atoms CG1 and CG2 for
VAL and CD1 and CD2 for LEU.

We have noticed that the order of CG1 and CG2 (and CD1 and CD2) as they
appear in PDB files give improper dihedrals that are in the neighbourhood
of -30. As a result, during the course of energy minimization or early MD,
this dihedral angle gets flipped to around +30, significantly altering the
side chain geometry, energetics and subsequently the backbone
geometry. The solutions to this problem are rather simple:

	1. Switch the CG1 and CG2 in VAL and CD1 and CD2 in LEU before
generating the binary topology file.

	2. Change the GROMOS RTF files to reflect the correct improper
order.

	We are interested in knowing whether other GROMOS users have
encountered this problem, or whether this is mentioned anywhere in the
GROMOS manual. We have checked the RTF files for GROMOS86 as well as
GROMOS87 and both contain the same ordering. 

	In all trial runs we notice that the improper dihedral flips
almost immediately and that in the specific case of lysozyme, the backbone
RMS difference between the incorrect and correct ordering can be as much
as .5A within 50ps (which is considerable). In some other cases, we notice
that this does not have too much of an effect. It is all a function of how
many VAL and LEU the protein has.

	Any comments and/or clarifications are appreciated.

Bill Harte, Bristol-Myers Squibb Pharmaceutical Research Institute 
G. Ravishanker, Dept. of Chemistry, Wesleyan University.

****************************************************************************
* Ganesan Ravishanker			Ph: (203) 344-8544 Ext. 3110       *
* Coordinator of Scientific Computing,  Fax:(203) 344-7960                 *
* Adjunct Associate Professor(Dept. of Chem.)                              *
* Wesleyan University               e-mail:[email-masked]  *
* Middletown, CT 06457.                                                    *
****************************************************************************

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From: [email-masked] (Tim Harvey)
Date: Tue, 23 Nov 1993 10:42:27 -0500

I think it's been known for a long time (almost since it was actually created)
that the GROMOS definition is opposite to IUPAC. It is mentioned in the GROMOS
manual;  section 4.2. Obviously having the Leu and Val chiral carbons invert
during a run is going to have significant effects.

Tim, who checks every line in GROMOS topology files by hand.