Nonstandard residues prep
This tutorial is created by and for AMS536 class at Stony Brook University and made available for the use of the whole modeling community.
The following are examples of a work flow of how to assign parameters for non-standard residues compatible with the amber program. This procedure will give you reasonable parameters; however, the charge calculation should use higher levels of theory and the other parameters should be optimized Further perhaps fit to QM or optimizing to reproduce experimental observables. Parameters assigned from gaff.
Fluorophenylalanine
To prepare the mutant structure for Molecular Dynamics, a copy of the phenylalanine residue from the raw pdb file for 1QP6 was made and subsequently modified using a text editor to include the name FPH, rather than PHE. Furthermore, the five hydrogen atoms on the phenylalanine residue named ‘H’ for hydrogen, were replaced with five F’s, for fluorine. Using the program, Chimera, hydrogens were added to this modified residue and the C-F bond length was defined as 1.35 Angstroms. Also using Chimera, which has a built-in antechamber module, charges were assigned using the charge model, AM1-BCC. The .mol2 file generated was used as an input to create a new pdb file and a prep file. Using Parmchk, the prep file, which establishes connectivity between atoms, was used as an input to create the frcmod file, which stores additional parameters. The prep file was manually modified to contain AMBER parameters from the PHE.prep file in the AMBER library for the backbone atoms of the mutant residue. The resulting structure is a hybrid of the two force fields(FF99SB for the backbone, whose parameters were taken from a PHE backbone, and GAFF for the side-chain), and for this reason, additional parameters, including the bond lengths, angles, and dihedral angles had to be specified and stored in the frcmod file. A Table of Additional Parameters (bond angles)stored in the frcmod file is shown below.
Angle Kθ θ Source c3-CT-C 63.8 110.53 GAFF: c-c3-c3 H1-CT-c3 46.4 110.05 GAFF: c3-c3-ha CT-c3-hc 46.4 110.05 GAFF: c3-c3-ha CT-c3-ca 62.5 114.61 GAFF: c3-c3-ca N-CT-c3 80.0 109.70 PARM99: CT-CT-N
Below is the prep file created:
FLUOROPHENYLALANINE molecule.res
FPH INT 0 CORR OMIT DU BEG 0.00000 1 DUMM DU M 0 -1 -2 0.000 0.000 0.000 0.00000 2 DUMM DU M 1 0 -1 1.449 0.000 0.000 0.00000 3 DUMM DU M 2 1 0 1.522 111.100 0.000 0.00000 4 N N M 3 2 1 1.335 116.600 180.000 -0.41570 5 H H E 4 3 2 1.010 -10.200 0.000 0.27190 6 CA CT M 4 3 2 1.449 121.900 180.000 -0.00240 7 HA H1 E 6 4 3 1.090 -109.50 300.000 0.09780 8 CB c3 3 6 4 3 1.533 110.759 -133.834 -0.01010 9 HB2 hc E 8 6 4 1.090 112.115 -149.730 0.08300 10 HB3 hc E 8 6 4 1.090 111.978 -26.211 0.08300 11 CG ca S 8 6 4 1.505 109.715 91.984 -0.10820 12 CD1 ca B 11 8 6 1.410 119.856 69.106 0.12160 13 FD1 f E 12 11 8 1.350 119.921 -0.168 -0.10880 14 CE1 ca B 12 11 8 1.410 120.090 179.880 0.07260 15 FE1 f E 14 12 11 1.350 120.094 -179.943 -0.10190 16 CZ ca B 14 12 11 1.410 119.913 0.059 0.09970 17 FZ f E 16 14 12 1.350 119.912 179.922 -0.09840 18 CE2 ca B 16 14 12 1.414 120.110 -0.071 0.07280 19 FE2 f E 18 16 14 1.350 120.153 -179.940 -0.10140 20 CD2 ca S 18 16 14 1.412 119.865 0.062 0.12490 21 FD2 f E 20 18 16 1.350 119.987 179.997 -0.10980 22 C C M 6 4 3 1.522 111.100 180.000 0.59730 23 O O E 22 6 4 1.229 120.500 0.000 -0.56790
LOOP
CG CD2
IMPROPER
-M CA N H CA +M C O CG CE2 CD2 FD2 CD2 CZ CE2 FE2 CE1 CE2 CZ FZ CD1 CZ CE1 FE1 CG CE1 CD1 FD1 CD1 CD2 CG CB
DONE STOP
non-starandard Nuclaic acids with modified backbone
PLEASE ADD DISCRIPTION
