Questions and problems?

Improper torsions

I found that the impropers defining the plane of the five-member ring in Histidine (HID) residue are not in file. This ring is supposed to be planar. Could you tell me what happens?

Rings in the united atom force field generally do not have impropers (see PHE and TYR as well). That's the way it has always been.....I don't know if it is the best solution or not. The planarity is maintained by the bond and angle terms.

Since Leap generates improper torsions based on atom types instead of using explicit lists of atoms in the residue topology file, I've noticed that extra impropers are added to PHE and TYR residues with the 91 forcefield that are not in 'db4.dat' and are therefore not generated by using Link-Edit-Parm.> These added impropers can add 3-10 kcal/mol for a moderately distorted system. Is there a quick workaround ?

When the Weiner et al. (1984,1986) force field was developed, improper torsions were designated for specific sp2 sites, as well as for united atom CH groups - sp3 carbons with one implicit hydrogen. In the sp2 case, the purpose is to make it harder to move out of plane, while for sp3, the improper was used to prevent inversion of the stereochemistry.

However, not every sp2 atom had an improper applied in the PREP file. When Leap was developed, a decision was made to have the program automatically flag each sp2 atom and check if an applicable improper torsion parameter could be found in the force field - similar to the method used to apply other parameters such as bonds, except that "missing parameters" are tolerated. To prevent impropers with "wild card" atoms from being applied inconsistently with the original "Prep version" of the force field, all such terms were replaced by specific impropers in a special "Leap version" of parm91.dat, parm91X.dat. However, it was impossible to force exact equivalence, since in the "Prep version," impropers had not been applied in a topologically consistent way to the TRP, PHE and TYR residues. We settled for allowing Leap to apply the reported impropers to PHE and TYR (which makes these residues more consistent with TRP), since (1) the new force field was in preparation and contains various adjustments to torsions and impropers that go beyond this issue, (2) we did not want to revise something that had been in the literature for a long time, and (3) except for highly distorted structures, which would be cleaned up by minimization and dynamics anyway, the properties of simulations should be very little affected (as we pointed out in Cornell et al. (1995), part of the floppiness that has been observed in Weiner et al. aromatic residues is due to a too small proper torsion potential for a aromatic C-C bond). Nonetheless, persons publishing papers using the Weiner et al. force field with leap topology generation should explicitly state this in the methods section of their papers.

In developing the Cornell et al. force field, we ensured that all the impropers were specified in a topologically consistent way in the "Prep version," which guarantees consistency with Leap.

I have compared the way improper torsions of aromatic acids (and of the bases of nucleic acids) are defined within the old and the new force field. With the new force field around every ring-atom which has a exocyclic substituent exactly one improper torsion is defined. Is this a general rule which can be applied in developing parameter-files for new residues with aromatic rings? I want the new residues to be defined in a way consistend to the existing residues.

Yes, all sp2 atoms should have an far we have developed those for C=O, N-R and C-R groups, where N is an amide nitrogen and C an sp2 carbon...thus, for example, it would be reasonable to use the same torsional potential for a new residue for any sp2 carbon-exocyclic substituent(C-R) as we have used for all the cases this occurs in the peptide side chains and nucleic acid bases.