Molecular Mechanics (MM) and Force Field Methods

 

Molecular Mechanics (MM) and Force Field Methods

What is Molecular Mechanics?

Molecular Mechanics (MM) is a computational method used to study molecules by applying classical physics laws instead of quantum mechanics.  OR

Molecular mechanics is a computational method that calculates molecular structure and energy using classical mechanics and force field equations without explicitly considering electrons.

Basic Assumptions of Molecular Mechanics

In MM:

1.      Molecules follow classical mechanics, not quantum mechanics.

2.      Atoms are point masses with fixed charges.

3.      Bonds behave like springs.

4.      Molecular energy depends on atom positions.

Because electrons are not explicitly treated, MM cannot describe:

Ø  Bond breaking or formation,

Ø  Electronic transitions,

Ø  Reaction mechanisms.

What is a Force Field?

A force field is a collection of equations and parameters used to calculate molecular energy.

It defines:

Ø  How atoms interact,

Ø  How bonds stretch or bend,

Ø  How atoms attract or repel each other.

Each force field is parameterized using:

Ø  Experimental data

Ø  Quantum chemical calculations

Total Energy Expression in Molecular Mechanics

Total molecular energy is the sum of different energy contributions:

Total Energy =

Ø  Bond stretching energy

Ø  Angle bending energy

Ø  Torsional (dihedral) energy

Ø  Non-bonded interactions

Components of Force Field Energy

(a) Bond Stretching Energy

Energy changes when the bond length changes from equilibrium.

Example: stretching a spring increases energy.

Depends on:

·         Bond length

·         Bond strength

In HCl molecule, hydrogen and chlorine atoms are connected by a bond having an equilibrium length (~1.27 Å).

If the bond is:

·         Stretched → energy increases.

·         Compressed → energy also increases.

Just like stretching or compressing a spring requires energy.

Opening or closing scissors away from natural position requires force.

(b) Angle Bending Energy

Energy changes when bond angles deviate from normal values.

Example: bending H–O–H angle in water.

The normal H–O–H angle is 104.5°.

If angle changes to:

·         100° or 110°
energy increases.

Because atoms resist angle distortion.

(c) Torsional (Dihedral) Energy

Energy changes due to rotation around bonds.

Example:
Ethane rotation causes energy changes due to steric interactions.

Important for conformational analysis.

Rotation occurs around the C–C bond.

Two important conformations:

1.      Staggered conformation

o    Lowest energy

o    Hydrogen atoms are far apart.

2.      Eclipsed conformation

o    Highest energy

o    Hydrogen atoms overlap, causing repulsion.

Ø  Ethane

Ø  Butane (anti and gauche forms)

Ø  Protein backbone rotations

 

(d) Non-Bonded Interactions

Interactions between atoms not directly bonded.

Includes:

i. Van der Waals interactions

·         Weak attraction or repulsion between atoms

·         Important for molecular packing

Example: Noble gas atoms

Argon atoms attract weakly at moderate distances but repel at very short distances.

Example in biology

Protein folding depends on van der Waals packing.

Example in materials

Layer stacking in graphite.

ii. Electrostatic interactions

·         Attraction or repulsion between charged atoms

·         Important in proteins and ionic compounds

Example: Na⁺ and Cl⁻ ions

Opposite charges attract strongly.

Example in molecules

Water molecules attract due to partial charges on O and H atoms.

Example in proteins

Charged amino acids interact.

Types of Popular Force Fields

Commonly used force fields:

·         AMBER – proteins, nucleic acids

·         CHARMM – biomolecules

·         OPLS – organic molecules

·         MM2/MM3/MM4 – organic compounds

·         GROMOS – biomolecular simulations

Each force field is optimized for certain molecules.

Applications of Molecular Mechanics

Molecular mechanics is widely used for:

✔ Geometry optimization
✔ Conformational analysis
✔ Molecular dynamics simulations
✔ Protein structure studies
✔ Drug design
✔ Polymer and material studies

Best suited for large systems.

Advantages of Molecular Mechanics

·         Very fast calculations

·         Suitable for large molecules

·         Low computational cost

·         Good for structural predictions

Limitations of Molecular Mechanics

·         Cannot study chemical reactions

·         Cannot describe bond breaking/forming

·         No electronic information

·         Accuracy depends on force field parameters

Typical Workflow in Molecular Mechanics

1.      Build molecular structure.

2.      Select appropriate force field.

3.      Minimize energy (geometry optimization).

4.      Perform simulations or analysis.