Dear Alexey,

Most molecular mechanics programs include non-physical terms for special systems such as e.g. hexane.

There are several ways in which out-of-plane bending terms can be incorporated into a force field. Usually, there are penalty energies for improper bending -measured with respect to certain observed geometry. AMBER should include those type of terms for describing adequately the cyclobutane geometry.

Expanding on Dr. Bohorquez’s answer - yes, the Amber force-field equation has the ability to model cyclobutane’s ring flexing and out-of-plane global minimum. This is done by the following three torsion terms: C-C-C-C, C-C-C-H, and H-C-C-H, where the atom types, bonded and nonbonded parameters will be dependent upon the force field employed.

I quickly checked to see how well Amber’s parm99SB and gaff force field perform, and both of them predict the wrong minimum by 15 degrees. Given that the ring conformation is described by the four C-C-C-C torsion angles, the minimum geometries have angles of +/- 18 degrees (due to symmetry) as computed by HF/6-31G(d)//HF/6-31G(d) theory. Parm99SB and gaff predict the minimum conformation to have values of 0 degrees and +/- 30 degrees, respectively. While gaff does predict a nonplaner geometry, parm99SB does better at predicting the repulsive portion of the curve than gaff. Gaff overestimates the barrier between the symmetrically equivalent minima by approximately 4 kcal/mol.

I have attached two images that provide the HF/6-31G(d)//HF/6-31G(d) (i.e. COPT), MP2/aug-cc-pVDZ//HF/6-31G(d) (i.e. HLSP), and Force-Field (i.e. Sander) comparison of the relative potential energy curves and the geometric RMSD.

If you wish to optimized the C-C-C-C, C-C-C-H, and H-C-C-H Amber torsion parameters for cyclobutane, you are welcomed to use Wolf2Pack (www.wolf2pack.com).[1,2] Wolf2Pack is free for academic use, and contains many other molecules for parameter investigation. Please note that the parameters for cyclobutane are fundamental to many chemical and biological systems, so changing them will have some impact if you model the molecule in combination with another entity or molecular fragment.

1. D. Reith and K.N. Kirschner, A modern workflow for force-field development – Bridging quantum mechanics and atomistic computational models, Comput. Phys. Commun., 182 (2011) 2184-2191.

2. Ottmar Krämer-Fuhrmann, Jens Neisius, Niklas Gehlen, Dirk Reith, and Karl N. Kirschner, Wolf2Pack – Portal Based Atomistic Force-Field Development, J. Chem. Inf. Model., 53 (2013) 802-808.

Thank you for your detailed answer.

However, I could not use Wolf2Pack. Something strange here. It produces a force field with hetero atoms.

WOLF2PACK supplementary derived parameters for the Parm99SB force field.

MASS

DU 1.008 0.616 Dummy atom

H 1.008 0.161 H bonded to nitrogen atoms

BOND

DU-DU 345.8 1.086 Dummy atom bond

C -H2 375.9 1.106 Taken from C-H1, validated for formamide and N_methylformamide - KNK

ANGLE

DU-DU-DU 100.0 104.52 Dummy atom angle

H2-C -N 45.0 112.00 Formamide - KNK

H2-C -O 50.0 122.00 Formamide, N-ethenylformamide - KNK

CA-C -O 50.0 125.32 Methyl-pyridine-2-carboxylate, KNK

CA-C -OS 50.0 109.00 Methyl-pyridine-2-carboxylate, KNK

DIHEDRAL

DU-DU-DU-DU 1 0.00 0.0 -1. Dummy atom torsion

1 0.00 0.0 -2.

1 0.00 0.0 3.

H2-C -N -H 1 0.00 0.0 -1. Formamide - KNK

1 -0.50 0.0 -2.

1 0.00 0.0 3.

IMPROPER

DU-DU-DU-DU 10.0 180. 2. Dummy atom improper torsion

H2-N -C -O 20.0 180. 2. Formamide

NONBON

DU 0.6000 0.0157 Dummy atom Lennard-Jones

H 0.6000 0.0157 Ferguson base pair geom.

Hello Alexey,

I think you are referring to the force-field file that can be seen in the last step of W2P's workflow, correct? What is shown is a basic force-field file with the correct format. The existing entries are there to provide a template for the terms that you should add - the ones that you are interested in. You can delete or add entries to this file as you desire. Alternatively, you can copy and paste the frcmod file for cyclobutane, which is given as output by antechamber if specified to do so. (This should be explained in the Knowledge Module #4: Optimizing missing parameters - parm99SB and cysteine sulfonic acid.)

Please use W2P's Message Board if you have further trouble.

Best regards,

Karl