Molecular Modeling

I. What is modeling?
 
• Model:
• Mathematical system that mimics a real object.
• Geometric model => graphics.
• Algebraic model => energy, forces.
 
• An event can be simulated from study of the model
• Graphics  => Structure variation.
• Energy or forces => Ligand-protein binding
• Time evolution of model => Conformation change, chemical reactions.

II. Modeling based on graphical analysis:

 

• Molecular shape and function.
 
• 3D conformation change and its effect.
 
• Protein 3D structure predication based comparison with other known proteins (homology modeling).

 

Examples:

A. Ligand-Protein Binding as a Lock and Key Process.


B. Protein domain motion
 

Drug Binding Induced Conformation Change in Protein.
 
 
 
 
 
III. Molecular modeling based on energy analysis:
 

 

• Energy measures the ability to do work.
 
• Motion is associated with energy.
 
• There are two types of energy:
 
• Kinetic energy -- motional energy.
Kinetic energy is related to the speed and mass of a moving object. The higher the speed and the heavier the object is, the bigger work it can do.
 
• Potential Energy -- "positional" energy.
 

Potential energy description:



Water falls from higher ground to lower ground. In physics such a phenomenon is modeled by potential energy description:

Objects move from higher potential energy place to lower potential energy place.
 


 
Atomic motions in molecules are also modeled by this potential energy description.
 

 
• Different types of bond motions are modeled by different energy functions.
 
• Energy terms are additive.
 
• The total energy determines overall effect.

 
 
 
Energy terms for a molecule:
 
 
• There are four type of bond motions important in chemical compounds:
 
 
• The total energy of motions is:

Energy = Stretching Energy +
               Angle Bending Energy +
               Torsion Energy +
               Non-Bonded Interaction Energy