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• Collection of atom types (to define the atoms in a molecule), parameters (for bond lengths,
bond angles, etc.) and equations (to calculate the energy of a molecule)
• In a force field, a given element may have several atom types.
For example, phenylalanine contains both sp3-hybridized carbons and aromatic carbons.
C-C bond in the ethyl group differs from a C-C bond in the phenyl ring
C-C bond between the phenyl ring and the ethyl group differs from all other C-C
• Total energy of a molecule is divided into several parts called force potentials, or potential
energy equations.
• Force potentials are calculated independently, and summed to give the total energy of the
molecule.
Examples of force potentials are the equations for the energies associated with bond
stretching, bond bending, torsional strain and van der Waals interactions.
These equations define the potential energy surface of a molecule.
Introduction to Molecular Modeling Techniques
Potential Energy Equation (Bonds Length)
• Whenever a bond is compressed or stretched the energy goes up.
• The energy potential for bond stretching and compressing is described by an equation
similar to Hooke's law for a spring.
• Sum over two atoms
Plot of Potential
Energy Function
for Bond Angle
Introduction to Molecular Modeling Techniques
Potential Energy Equation (Improper Dihedrals)
• As the improper dihedral is bent from the norm, the energy goes up.
• Sum over four atoms
Plot of Potential
Energy Function
for Improper
Dihedrals (ω o = 0)
Introduction to Molecular Modeling Techniques
Potential Energy Equation (Dihedral Angles)
• As the dihedral angle is bent from the norm, the energy goes up.
• The torsion potential is a Fourier series that accounts for all 1-4 through-bond
relationships
• Sum over four atoms
… Fourier Series
Multiple minima
Introduction to Molecular Modeling Techniques
Potential Energy Equation (Dihedral Angles)
• Need to include higher terms non-symmetric bonds
Distinguish trans, gauche conformations
atoms ~r6
When atoms get too close, valence shell start to overlap and
repel ~r12
Than becomes
repulsive
Interaction first
attractive
Introduction to Molecular Modeling Techniques
Long-range forces
Coulomb’s Law
Coulomb’s Law
ε
protein ~ 2-4
ε
solvent ~80
For protein calculations using NMR constraints, typically
of calculations.
With electrostatics off during the structure
How do you bring distant regions of the primary chain into contact?
Nrestra int s
EHB = kHB ∑ (1
m =1
/ R 3
− A − [ B /{2 . 07 + cos φ 3 2
NHO} ])
What Relationship Does This Energy Value Have to Any Experimental Observation?
NOTHING!
The energy value simply indicates how well the structure conforms to the expected parameters.
C C
Want to Keep All Known Geometric Values Distance constraint is satisfied (improperly)
Within Proper Ranges with large distortion in bond lengths
Introduction to Molecular Modeling Techniques
Molecular Minimization starting from some structure (R), find its potential energy using the
potential energy function given above. The coordinate vector R is then varied using an optimization
procedure so as to minimize the potential energy ETOTAL(R).
if each residue has only 3 possible conformations (far less than reality)
In order to properly refine this poor structure, the minimization protocol would need to pull
the Cδ back through the ring which would require first going to a higher energy structure.
This will not occur since the trend for minimization is to move towards a lower energy.
The “minimized” structure will probably result with a stretched and distorted Cδ-Cγ
bond as it moves the Cδ away from the ring from the other direction
the benzene ring and the remainder of the Leu side-chain will also be distorted in an
One measure of the distance from a stationary point is the rms gradient:
Introduction to Molecular Modeling Techniques
Molecular Minimization
• Process Overview
minima occurs when the first derivative is zero and when the second derivative is positive.
the coordinates at step n+1 are determined from coordinates at previous step n
the initial step is a guess
a systematic or random search is not practical (Levinthal Paradox)
current step vector is not similar to previous step vectors
accumulates information about the energy function from one iteration to the next
follow the laws of classical mechanics, most notably Newton's Second law:
The force on atom i can be computed directly from the derivative of the potential energy
function (U) with respect to the coordinates ri, Fi = -δU/δri.
to initiate MD we need to assign initial velocities
This is done using a random number generator using the constraint of the Maxwell-
Boltzmann distribution.
where:
Hamiltonian H(Γ) where Γ represents the set of positions and momenta
Target Temperature (T)
Boltzman constant (kB)
Introduction to Molecular Modeling Techniques
Molecular Dynamics (MD)
The temperature is defined by the average kinetic energy of the system according to the
kinetic theory of gases.
– internal energy of the system is U = 3/2 NkT
– kinetic energy is U = 1/2 Nmv2
where :
N is the number of atoms
v is the velocity
m is the mass
T is the temperature
k is the Boltzman constant
By averaging over the velocities of all of the atoms in the system the temperature can
be estimated.
Maxwell-Boltzmann velocity distribution will be maintained throughout the
simulation.
• If system has been energy minimized potential energy is zero and temperature is zero
• Need to “heat” system up to desired temperature
scale velocities: v = (3kT/m)1/2
• Calculate a trajectory in a 6N-dimensional phase space (3N positions and 3N momenta)
measure trajectories in small time steps, usually 1 femto-second (fs)