1. Amber: How to Prepare Parameters for Non-standard Residues

2. Requirements
Amber Modules: xleap/tleap, antechamber, parmchk, Gaussian (not a part of Amber)
Molecule Editor
Text Editor

3. Parameter Preparation Workflow Using Gaussian
Structure
Output with
ESP Info
Text Editor
Gaussian
antechamber
Residue
Structure
parmchk
prepin file
frcmod file
Molecule Editor
Xleap/tleap
Lib File

4. Molecular/Structure Editors
Freeware (not many)
Xleap (very basic editor facilities)
Sirius sirius.sdsc.edu/
JMolEditor sf.anu.edu.au/~vvv900/cct/appl/jmoleditor/index.html
Commercial Software
Sybyl, HyperChem, Spartan, GaussView, etc.

5. Parameter Derivation

6. Parameter Derivation: Partial Charges
QM = ab initio, DFT, semi-empirical

7. Parameter Derivation: Van der Waals Parameters
It is the most difficult part…
1) Optimizing van der Waals parameters to reproduce the experimental or high-level Quantum Chemical data
Could be computationally expensive
2) Optimizing van der Waals parameters through the Monte Carlo or MD simulations to reproduce the experimental properties of bulk solvent (density, etc.).
For example, OPLS van der Waals parameters
Could be computationally expensive
3) Reusing existing van der Waals parameters for similar atom types from the same or other force field
The simplest approach

8. Parameter Derivation: Bond and Angle Interactions
req and θeq come either from experimental data (X-ray, neutron diffraction) or Quantum Chemical calculations (geometry optimization)
Kr and Kθ force constants are usually optimized to reproduce the vibration frequencies calculated using high-level Quantum Chemical methods.
Or (the simplest approach)
Kr and Kθ force constants could be derived from the existing bond/angle parameters for similar bond/angle types from the same or other force field

9. Parameter Derivation: Dihedral Angle Interactions
Vn, n, and γ are derived to reproduce the rotational profile from the high-level Quantum Chemical calculations.
Or (the simplest approach)
Vn, n, and γ could be derived from the existing dihedral angle parameters for similar dihedral angle types from the same or other force field
J.Wang et al., Development and testing of a general amber force field, Journal of Computational Chemistry, 25 (2004), 1157

10. Parameter Preparation Workflow Using Gaussian
Output with
ESP Info
Derived
Parameters
antechamber
parmchk
prepin file
frcmod file
Parameter modification file
Xleap/tleap
Lib File
Description of residue(s)

11. Appendix

12. Inhibitor covalently bonded to the Ser-195 of a protein

13. SEP (Ser-195)
PPH