Amber: How to Prepare Amber: How to Prepare Parameters for Parameters for Non-standardNon-standard

ResiduesResidues

RequirementsRequirements

1. Amber Modules: xleap/tleap, antechamber, parmchk, Gaussian (not a part of Amber)

2. Molecule Editor

3. Text Editor

Parameter Preparation Workflow Parameter Preparation Workflow Using GaussianUsing Gaussian

Structure

Xleap/tleap

Text Editor

ResidueStructure

prepin file

Lib File

Gaussian

Output withESP Info

Molecule Editor

antechamber

parmchk

frcmod file

Molecular/Structure EditorsMolecular/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.

Parameter DerivationParameter Derivation

Parameter Derivation:Parameter Derivation: Partial ChargesPartial Charges

QM = ab initio, DFT, semi-empirical

Parameter Derivation: Parameter Derivation: Van der Waals ParametersVan 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

Parameter Derivation:Parameter Derivation: Bond and Angle InteractionsBond 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

Parameter Derivation:Parameter Derivation: Dihedral Angle InteractionsDihedral Angle Interactions

Vn, n, and γ are derived to reproduce the rotational profile from the high-level Quantum Chemical calculations.

J.Wang et al., Development and testing of a general amber force field, Journal of Computational Chemistry, 25 (2004), 1157

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

Parameter Preparation Workflow Parameter Preparation Workflow Using GaussianUsing Gaussian

Xleap/tleap

prepin file

Lib File

Output withESP Info

antechamber

parmchk

frcmod file

Description of residue(s)

Parameter modification file

DerivedParameters

Appendix

Inhibitor covalently bonded Inhibitor covalently bonded to the Ser-195 of a proteinto the Ser-195 of a protein

SEP (Ser-195)

PPH