Download Atomic and molecular models for macromolecular structure

Atomic and molecular models for
macromolecular structure
Molecular Modeling
Molecular Mechanics / Force Fields
• Computational model
• Atomic framework for macromolecular structure
• Full quantum mechanics is not possible
• Classical forces between atoms
• Minimize energy to obtain structure
Force Field
• CHARMM, OPLS, GROMOS, AMBER
• Each atom has
– Position, charge, mass, perhaps polarizability
– Radius, Bonding accounted for in energy function
• Account for bonding and non-covalent interactions:
Etotal  Ebonded  Enonbonded
Bonding and Nonbonding Interactions
• Bonded interactions have simple
constraints for configuration in
1D, 2D, and 3D
Ebonded  Ebonds  Eangles  Edihedrals
• Non-covalent or through space
Enonbonded  Eelectrostatic  Evan derWaals  Erepulsion
• Sometimes extra terms
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Dipole-Dipole
Hydrogen Bonds
-conjugation
Anharmonicity
Fixing problems…
The Force Field Potential Energy
Rmin
+ repulsion (r-12)
http://amit1b.wordpress.com/computational-biophysics/
Parameterization
• Force Fields are Empirical or Semi-Empirical
• Empirical: Parameterized to match experiment
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Thermodynamic data (Hform)
Dipole moments
Known molecular structure
Vibrational frequencies
• Semiempirical:
– Parameterized from ab initio calculations
• Self-consistent analysis of data
SPC/E water (Simple Point Charge Extended)
• Point charges for O, H
• Lennard-Jones Potential
http://www1.lsbu.ac.uk/water/water_models.html
Examples of other models
• “Knowledge Based” statistical models
– Free energy drawn from known statistics: F = -kT lnP
– For instance: Statistically determined  angles.
QM/MM
(Quantum Mechanics/Molecular Mechanics)
• For study of processes where quantum mechanical
effects are crucial (i.e. enzymatic catalysis)
• Divide space into two regions
Quantum and
Classical
Spaces interact
mechanically and
electrostatically:
Classical
(MM)
Quantum
(QM)
H  H QM  H MM  H QM / MM
Coarse Grained Models
• Cross-over from atomic to physical models
• Beads with springs
– 1-6 for amino acids
– Beads for proteins
• Multiscale models