This document discusses molecular mechanics force fields, specifically the Merck Molecular Force Field (MMFF). It provides details on the functional form and parameters of MMFF, including that it is a Class II force field designed to accurately model conformational energies and non-bonded interactions of pharmaceutical compounds. The total energy expression for MMFF is provided, including terms for internal interactions like bonds, angles, and torsions, as well as nonbonded van der Waals and electrostatic terms. Application of MMFF in the CHARMM program is also described.

1. Submitted by: seema
Class: M.Sc. Bioinformatics
Roll no. 1010
M.D.University Rohtak

2. Some general feature of molecular
mechanics force field
 Must specify functional form and parameters
 Should be constructed as single entity
 Some terms sufficiently independent of the others (bond
and bond angle)
 Primarily designed to reproduce structural properties but
can also used to predict other properties, such as molecular
spectra
 Transferability of functional form and parameters
 Comprise between accuracy of functional form and
computational efficiency
 Atom type

3. MMFF: A Class II force field designed to be a transferable
force field for pharmaceutical compounds that accurately
treats conformational energetic and non bonded
interactions. This would, ideally, produce a force field that
was adequate for both gas phase and condensed phase
calculations.
Classes of force field:
Class I: Simplicity of form of the potential energy function
limits transferability.
Class II: Extended potential energy function, including cross
terms, increases transferability.

4.  MMFF Total energy
 Internal terms: bonds, angles, stretch-bend, out-of-
plane bending and dihedrals
 Nonbonded terms: van der Waals and Electrostatic.
 initial published version is "MMFF94”.
 MMFF93 collaborate in CHARMm and are working to
make MMFF94 available in CHARMM
 currently being implemented in the BatchMin module
of the MacroModel program suite.

5. Form of the Merck Molecular Force Field
The MMFF94 energy expression can be written as :
EMMFF = ΣEBij + ΣEAijk + ΣBAijk + ΣEOOPijk;l + ΣETijkl +
ΣEvdWij + ΣEQij
EBIJ = Energy of bond stretching
EAIJK = Energy of angle bending
EBAijk =Energy of stretch-bend interaction
EOOPijk;l = Energy of out-of-plane bending
ETijkl =Energy of torsion interaction
EvdWij = Energy of van dar waal interaction
EQij = Electrostatic interactions

9.  Application of MMFF in CHARMM
1) Open and read “topology” and parameter files
2) Structure input
Merck format files (*.mrk)
Mol2 format
Single molecules
MOL2 databases
CHARMM format
 3) Be careful to use proper treatment of nonbond
interactions

10.  MMFF capabilities in CHARMM
 Energy, minimization, dynamic simulations
 Structural analysis
 Dynamic analysis (excluding energies via correlation
module)
 Vibrational analysis
 Free energy perturbation
 limited by requirement of “chemical correctness”
 internal coordinate perturbation via TSM
 chemical perturbation via PERT, see CHAR