MolecularModelling Unit 3 v2

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Computational Modelling in Physics,

Chemistry and Biochemistry
Molecular Modelling
Unit 3. Classic Model
Juan Torras, Univ. Politècnica Catalunya (2015)
Contents
 3.1. Molecular Interactions Modelling
 3.2 Bond Stretching
 3.3 Angle Bending
 3.4 Torsional Terms
 3.5 Improper Torsions
 3.6 Non-bonded interactions
 3.6.1 Electrostatic Interactions
 3.6.1.1 Multipole expansion
 3.6.1.2 Point-charge models
 3.6.1.3 Charge Derived from the Molecular Electrostatic Potential
 3.6.1.3.1 RESP charges
 3.6.1.4 Distributed Multipole Models
 3.6.1.5 Using Charge schemes to study inter-molecular interactions
 3.6.1.6 Polarization
J.Torras - UPC (2015) Molecular Modelling - Computational Modelling in Physics, Chemistry and Biochemistry
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Contents
 3.6.2 Van der Waals Interactions
 3.6.2.1 Dispersive Interactions
 3.6.2.2 Modelling Van der Waals Interactions
 3.6.3 Molecular Modelling of Hydrogen Bonding
 3.7 Force Field Models
 3.7.1 All Atom versus United Atom
 3.7.2 Force Field Parametrization
 3.7.3 Transferability
 3.8 Periodic Boundary Condition
 3.9 Truncation of non-bonded terms
 3.9.1 Van der Waals Potential
 3.9.2 Long-range electrostatic
 3.9.2.1 Ewald’s Summation
 3.10 Introduction to the GROMACS, AMBER, and CHARMM
Packages
3. Classic Model
 Origin
 1930´s D.H. Andrews develops the mechanic model of the
molecule.
 A molecule is described as a set of masses connected by bonds
 If it is known the total system energy  Interactions between its
masses
 Any conformational change in the molecule  disturbance in the computable
energy
 Extended use of classic mechanics methodologies
 Computational limitations of quantum mechanics formalism to
study multiatomic systems
 The initial goal is the Minimization of the steric energy
 Description of van der Waals interactions and bond geometry
deformation
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3. Classic Model
 System of N molecules
 Within Born-Oppenheimer approximation
 The rapid motion of electrons have been averaged out
 Hamiltonian of the system depends on coordinates
and momenta of each molecule
, ,…,
, ,…,
,
3. Classic Model
 Kinetic energy
, ,
2
 Potential energy
 The energy is divided into terms depending on the coordinates of
individual atoms, pairs, triplets, etc
, , , …
 is the most important

  up to 10% of the lattice energy of argon
 Important in liquid phase
 Pairwise approximation  remarkably good description
 averaged three-body effects included within an “effective” pair potential
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3.1. Molecular Interactions Modelling

 Molecular mechanics
 Molecular interactions are calculated through classic potentials
 Inter and intramolecular potentials are approximately computed as the sum
of divers energy terms
 Inclusion of adjustable parameters
 It reproduce correctly the conformational behavior of organic molecules
 Model
 Atoms are represented by bulky spheres
 Mass and partial charge are defined
 Do not consider any specific electronic effect
 No electronic rearrangements can be studied
 chemical reactions, electronic transfer, etc.
 Conformational energy
 For each chemical species allegedly exist a set of natural bond angles and
distance to which the molecule tries to adapt its geometry, limited by its
structure and the present interatomic interactions

 The Harmonic approach
 The classic potentials were originally developed for the vibrational
analysis of molecules
 Based on the classical formalism when a molecule moved away from an
equilibrium point, which is the potential energy minimum, the potential
energy of this new state can be expressed through a Taylor series:
1
Vpot V0
2
,
1
…
6
, ,
 V0 corresponds to the energy minimum, thus can be set to 0, as

reference point
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 The Harmonic approach
 If we assume that the potential only depends on the first non zero
term (third term) we obtain the so called harmonic approach
1 1
Vpot ≅
2 2
,
,
 At the equilibrium distance we assume a minimum of potential energy
 which generally remains valid when the displacement form the

equilibrium coordinates is not too big
 The proportional constant is named Force Constant

 Correlating Force constant and experimental data
 Force constants would relate with experimentally measurable
magnitudes and they should reproduce the experimental values
 Stretching and bending  IR and Circular Dichroism
 Torsion  Microwaves Spectroscopy *
 Van der Waal radium  Apparent radii in crystal structures
 Data banks such as Cambridge Data Bank *
 Electrostatic charges  electron density measures
 X –Ray diffraction *
 If experimental data is not available then Quantum Chemistry
Ab Initio calculations need to be used to obtain reasonable to
good parameters.
 All parameters should be tested against a data set of known
molecules
* However most commonly obtained via fitting QM results
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 Force Field
 Set of classical analytical functions and empiric parameters that
allows computing the steric molecular energy of a determined
conformation.
 The empiric parameters are optimized from experimental and
theoretical properties
 Molecule geometry, conformational energy, formation heats, vibration
frequencies…
 The total energy of a molecular system is expressed as the
summation of different independent energy contributions
E E E

 Force Field
 Energy of bonded Interactions
 Potentials associated with the chemical bonds (“the harmonic
expressions”)
E E E E
 Depending on the complexity of the harmonic expressions there are two
classed of Force Fields
 Those that use simple expressions with only one term are know as class I
 Common in biomacromolecules FF  AMBER, CHARMM, OPLS, GROMOS…
 and those that used complex summations (that include non harmonic terms
and crossed terms as well) are known as class II
 Common in organic chemistry FF  Allingher’s MMn series, UFF…
 Energy of non-bonded interactions
 Potentials that correspond to the rest of physical interactions within
molecular systems
E E E
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 Force Field
 Bonded interactions
 Energy potentials terms directly related
with the structure of the chemical bond Torsion
Bond
 Stretching stretching
 Term related with the extension and
contraction of the bond distance respect
to an equilibrium distance
Angle
bending
 Bending
 Flexion of the bond angle respect to the Non-bonded interactions
most stable value
 Torsion
 Related with the rotation around chemical
bonds (dihedral angle)

 Force Field
 Non-bonded interactions
 Energy terms related with any intra-
and inter- molecular interaction that Torsion
does not implicate the chemical Bond
bond stretching
 Electrostatics
 Classic representation of the
interaction between the charge Angle
distribution of the atoms, which bending
includes polar and ionic interactions
Non-bonded interactions
 Van der Waals
 Energetic quantification of different
types of interactions, which share
their lack of electrostatic character
 The dispersion forces of London and
the repulsion between nuclei
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 Force Field
Michael Levitt, Nobel Lecture (2013)
3.2 Bond Stretching

 Morse potential
1
 It allows a bond dissociation ???
 Harmonic potential
 Quadratic equation (Hooke’s law) Hook
Morse
cubic
2
 Bond as a spring
 Minimum  equilibrium length
 Cubic potential 1 1.5
r0
2 2.5
 Allow a better approximation to Morse potential

1 …
2
 Anharmonic behavior  it takes more energy to compress a bond than it
does to stretch a bond the same distance. (Morse potential)
 Higher powers can be added to the harmonic equation to help simulate the
Morse function
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3.3 Angle Bending

 Harmonic Hook function
 Is the preferred choice to compute angle bending energy
 Is possible higher powers to the first order for very strained systems
(i.e. cyclopropane)
Ebend
Atom
C sp3 63.21 110.63
C sp2 69.84 121.81
C sp1 64.44 180.00
C arom. 67.18 119.97
k1=25
k2=50 Gaussian Amber Force Field
C-C-C bending parameters
k3=75
k4=100
Angle
110 115 120 125 130 bending
θ
3.4 Torsional Terms

 Cosine function
 Allows description of energy barriers associated with the
rotation around chemical bonds
 The origin of this potential goes beyond the simple
interpretation in terms of the vdw repulsion between atoms
in eclipsed conformations
 The contribution of the vdw repulsion is only about10%
 Most of its origin has not classical explanation since the
potential energy barriers of rotation are mostly due to
quantum effects between bonding and non bonding orbitals
 Periodic function based on cosines of torsional angle with
two parameters: Amplitude , and Phase
1 cos
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3.4 Torsional Terms

 Elaborated torsional barriers 1.5
V1=0.144; n=3; γ=0
 More complicated torsional barriers V2=1.175; n=2; γ=0

might be simulated by adjusting to a O‐C‐C‐O (V1+V2)
Fourier expansion of cosines, 1
reproducing satisfactorily QM rotation
Energy profiles.
 Most force fields use a single cosine with 0.5
appropriate barrier multiplicity, n 
Number of minimum points of energy
1 cos
0
0 60 120 180 240 300 360
θ
 Some use a Fourier expansion of cosines to correctly model the tendency
to adopt an specific conformation.
 O-C-C-O  adopt a gauche conformation (OH-CH2-CH2-OH)
1 cos ; cos
2
3.5 Improper Torsions

 Out-of-plane Bending motions
 Deformation of rigid bond geometries
 Movements out of the plane in molecules that usually present
conjugated π electrons
 Generally represented as a Fourier series or a sum of power
functions
1 cos 2 ;
2
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3.6 Non-bonded interactions

 Two main interactions
 Electrostatic interactions
 Coulomb potential
 Multipole expansion
 Van der Waals interactions
http://proteopedia.org/wiki/index.php/Cation-pi_interactions
PNAS, cover photography, September 17, 2002; 99 (19)
3.6.1 Electrostatic Interactions

 Coulombic potential
 Is the most common way of representing electrostatic
term in Molecular Mechanics
 Interactions of pair of particles holding a partial charge
http://proteopedia.org/wiki/index.php/Cation-pi_interactions
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3.6.1.1 Multipole expansion

 Some force fields compute the electrostatic term as
interaction between dipoles
 In this model the atom particles do not have net electric
charge
 The chemical bonds between different atom types present dipole
moments
 Magnitude depends on the kind of functional group each bonded
atoms belongs to.
 Electrostatic Energy is computed as the interaction energy
between charge-dipole, dipole-dipole, charge-quadrupole,
dipole-quadruple, quadrupole-quadrupole …

 The electrostatic potential at point P of a molecule made of two
charges at distance r from the origin
1
∅
4
 Expressing r1 and r2 in function of r and and expanding in a
Taylor’s series
1 cos Θ 3 cos 1
∅ …
4 2
P
 charge
 dipole r1 r2
Θ  quadrupole r
q1 θ q2
-z1 O +z2
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 Electrostatic interaction between two molecules is calculated by
multiplying each charge by the potential tat that point and adding
the result for each charge
E ,
1 ′ 1
4
′
2cos cos sin sin cos …
 Efficient to calculate E between molecules

 Is not applicable at molecular distances
 Sphere of charges representing a molecule
ξ
should not intersect with other interacting
molecule spheres
 Not useful for intramolecular interactions
3.6.1.2 Point-charge models

 One charge minimum for each atomic nuclei
 Accurate representation may require charges placed out of
atomic nuclei  several water models
http://w3.iams.sinica.edu.tw/lab/jlli/thesis_andy/node8.html
 We assume that if sufficient point charges are used then

all of the electric moments can be reproduced and the
multipole interaction energy can be approximated
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3.6.1.3 Charge Derived from the

Molecular Electrostatic Potential
 Atomic charges can be chosen to reproduce thermodynamic properties
 Only practical for small molecules
 Electrostatic properties are consequence of the distribution of the
electrons and the nuclei.
 Atomic charge is not an experimentally observable quantity
 Considerable debate about the best way to derive atomic charges
 Charges from Molecular Electrostatic Potential (MEP)
 MEP is an observable quantity  derived from wave function
 Obtain a set of partial charges that best describe the quantum mechanical
electrostatic potential at a series of points surrounding the molecule
 Symmetry condition can be imposed  charge of atoms symmetrically equivalents within the
molecule
 Trying to reproduce molecular dipole moment
 Minimize the function
 (QM potential) ; (Potential from set of points)

3.6.1.3.1 RESP charges

 Least squares algorithm derives atom centered charges
that best reproduces MEP Starting structure (PDB)
 Potential calculated on 4 shells of surfaces defined by {1.4,

1.6, 1.8, 2.0} x VDW radii (Singh & Kollman, J. Comput. Chem. 5
Perform Geometry
(1984)129 ) Optimization (HF-631G*)
 ESP at each point derived from QM

 Hyperbolic restraints on atoms  particularly buried Compute Electrostatic
Potential Charges (pop=mk)
atoms (RESP formalism: Bayly et al., J. Phys. Chem. 97 (1993) 10269 )
 Reduce high charges that can be assigned artificially in
standard electrostatic potential fitting methods Fit ESP charges (RESP)
MD simulation (AMBER)
Electrostatic potential
mapped in a isodensity
surface
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3.6.1.4 Distributed Multipole Models

 Allows to represent the anisotropy of a molecular
charge distribution .
 Point charge, dipoles, quadrupoles, etc. Are distributed
throughout the molecule
 Distribute Multipole Analysis (DMA)
 Stone & Alderton, Mol. Phys. 56 (1985) 1047
 Calculates the multipoles from a quantum

mechanics wavefunction
 DMA depend strongly on molecular conformation
multipoles would have to be recalculated at each
conformational change
 Includes non-spherical, anisotropic effects
 i.a. lone pairs and pi electrons
3.6.1.5 Using Charge schemes to study

inter-molecular interactions
 Molecules containing systems
 Different orientations
 Edge-on, T-shaped and face-to-face
 Hunter & Saunders (1990)
 Benzene molecule with three charge on C
 +1 on C and two -1/2 chare above and
below
 Charge-charge interaction  Coulomb’s law
 Very simple method that
 - repulsion dominates  face-to-face
 - attraction dominates  edge-on
 - attraction dominates  offset stacked
Hunter & Saunders, JACS 112 (1990) 1024

Andrew R. Leach.
Molecular Modelling.
Prentice Hall. 2001
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3.6.1.6 Polarization
 Usual FF’s do not account for electronic polarization of the
environment
 External electric field (neighboring molecules) induce a dipole in a
molecule,
-
- -- ++
- +
- +
 is the polarizability
 A third molecule can significantly reduce electrostatic interactions (size of
electric field) on the second molecule  Induction energy
 The energy of interaction between and E (induction energy) is
due to the work done in charging from 0  E
1
,
2
3.6.1.6 Polarization
 Main groups of methods including polarization effects in FF
 Fluctuating charge
 Based on the principle of electronegativity equalization: a charge flows between atoms
until electronegativities of the atoms become equalized. (CHARM)
 Drude oscillator (shell models)
 Atoms as a two-particle system: a charged core and a charged shell. The core and
shell are linked by a harmonic spring. (CHARM & GROMOS)
 Induced point dipole
 Classical point dipole approach  polarization energy is described as the
interaction between static point charges and the dipole moments they induce. (
OPLS/PFF, AMOEBA and AMBER ff02, ff02EP and ff02r1)
 Polarization treatment using continuum solvent (and solute)
 Continuum dielectric approach explicitly treat a molecule at the atomic level, and
the solvent or environment as a continuum medium, characterized by different
dielectric constants.
 Electronic polarization via quantum mechanical treatment or mixed QM/MM
 In the quantum mechanical region, electrons are explicitly treated and, so,
polarization effects are included in a natural way
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3.6.2 Van der Waals Interactions

 van der Waals energy ( ) can be
expressed as the sum of two forces
 Short distance: repulsive force
 Long distance: attractive force between
atoms
 potential has a single
minimum
 The interatomic distance in which the
function is minimal correlates with the
Van der Waals radium
 Depth of the minimum well is related r0
with the polarizability of the atoms
(interaction strength
 The slope of the well is the atomic
hardness, i.e., the energy tolerance to
overlap atomic spheres
3.6.2.1 Dispersive Interactions

 Attractive contributions
 Due to dispersive forces (London forces)
 Instantaneous dipoles which arise during the electron density
fluctuations  can induce dipole in neighboring atoms
 Drude Model
 Molecules with two charges +q and –q, separated by a distance r
 Negative charge is vibrating in harmonic motion with respect to
stationary positive charge
 Predicts that the dispersion interaction varies as r -6
3
4 4
 Only considers dipole-dipole interaction
 Higher-order terms  dipole-quadrupole , quadrupole-quadrupole, …
…
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3.6.2.2 Modelling Van der Waals

Interactions
 Lennard-Jones potential
 Most commonly used and easier to compute.
 Transferability  Lorentz-Berthelot mixing rules and
 However, it must be known that r -12 rises too rapidly compare to QM Energy
profiles (repulsive term)
EvdW 4ε ; ⁄2 ;
 Buckingham potential
 QM suggests exponential repulsion.
 This potential introduce an exponential repulsion term
 Hard to compute
 Adjusting parameter is a complex task
 Successfully computing crystals structures and ionic
species
 At very short distance  potential becomes strongly
attractive
https://en.wikipedia.org/wiki/Buckingham_potential
EvdW 6
6
3.6.3 Molecular Modelling of Hydrogen

Bonding
 Some force fields add an extra term
r
 Improves the accuracy in predicting the geometry of hydrogen-
bonding systems
 It requires that hydrogen bonds are identified before
performing the calculation
 other force fields just use a balance between electrostatic
and non-bonded terms
http://ww2.chemistry.gatech.edu/~lw26/structure/molecular_interactions/mol_int.html#E0
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3.6.3 Molecular Modelling of Hydrogen

Bonding
 Water models
 Rigid models
 fixed atom positions (match known geometry
of water)
 only non-bonded interactions
 Flexible models:
 Include bond stretching and angle bending
 Reproduce vibration spectra
 Polarizable models:
 include explicit polarization term
 Enhances ability to reproduce water in different
phases and interaction between them
 TIP3P & TIP4P
 Jorgensen et al, J. Am. Chem. Soc.105 (1983) 1407
 TIP5P
 Mahoney & Jorgensen, J. Chem. Phys. 112 (2000) 8910
 TIP6P
 Chen & Smith, J. Chem. Phys. 126 (2007) 221101
 SPC/E
 Berendsen et al, J. Phys. Chem. 91, 6269 (1987)
http://www1.lsbu.ac.uk/water/water_models.html
3.7 Force Field Models

 The number of non-bonded interactions scales with
the square of the number of interactions sites.
 Interactions sites tends to be reduced
 Subsume H atoms into atoms to which they are bonded
 Two main system representation
 All Atom
 All atoms in the system are considered
 United Atom
 Methyl group modelled as a single “pseudo-atom”
 Coarse-Grained
 Chemical groups and units are modeled as a single “pseudo-atom”
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3.7.1 All Atom versus United Atom

 United atom force fields
 Do not consider H atoms explicitly
 H atoms bonded to polar atoms (possible Hydrogen-bonds) are explicitly
represented
 Pros
 Several implementations: AMBER, CHARMM, GROMOS, …
 Reduce the effort by a factor ~2-3.
 Cons
 Chiral centers (in proteins) may be able to invert during a calculation
 Improper torsion term hast to be added to keep the side chain in the correct position
 The Van der Waals center is located at the carbon atom
 It does not reflect the presence of displaced hydrogen atoms
 The vdW term position should be offset slightly from C position
3.7.2 Force Field Parametrization

 PROTEINS:
 AMBER “Assisted Model Building with Energy Refinement” (Kollman/Case)
 http://ambermd.org/
 Main series: ff94, ff96, ff99, ff03, ff10
 Dihedral modifications: ff99sb, ff99sb-ildn, ff99sb-nmr, ff99-phi
 GAFF (Generalized AMBER force field) J. Comput. Chem. 25 (2004 ) 1157-1174
 OPLS “Optimized Potential for Liquid Simulation” (Jorgensen)
 OPLS-UA (united atom) J. Am. Chem. Soc., 110 (1988) 1657
 OPLS-AA (all atom) J. Am. Chem. Soc. 118 (1996) 11225-11236
 OPLS-AA/L (revised torsions)
 OPLS-2001, OPLS-/2005 (improved solvation free energies)
 CHARMM “Chemistry at Harvard Molecular Mechanics” (Karplus)
 http://www.charmm.org/
 CHARMM19 (united atom), CHARMM27 (all atom)
 CHARMM36 (carbohydrates)
 CMAP (two-dimensional dihedral corrections)
 CGenFF (General CHARMM force field) J. Comput. Chem. 31 (2010) 671–690
 AMOEBA “Atomic Multipole Optimized Energetics for Biomolecular
Applications”
 Contains polarizable point dipoles J. Phys. Chem. B 114 (2010) 2549–2564
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 MARTINI force-field
 Four-to-one mapping
 Four type of particles
 Polar, Non-polar, Charged,
and Apolar.
Non-Bonded interactions
Marrink et al., J. Phys. Chem. B 111 (2007) 7812-7824
Bonded interactions
Ring particles (2 or 3 to 1 mapping)

 Force Fields are largely
empirical
 You get so many parameters:
Make them fit experiment!
 Ab initio calculations can be
used
 How does one get charges?
 Small molecules (representatives)
where to obtain parameter from
QM simulations
 FF should be properly
validated by testing against
experimental data
 i.e. Thermodynamic data (solvation
energy), equilibrium conformations
and vibrational frequencies Lindorff-Larsen et al. PLoS ONE 7(2) (2012) e32131
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3.7.3 Transferability
 The modelling of systems containing mixtures of particles implies a bunch
of new parameters
 Those parameters have to be able to be “transferred” to new systems
 It is possible if all parameters are derived in the same way
 FF are developed to study:
 One atomic or molecular species under a wider range of conditions 
“general” FF
 An specific class of molecules: e.g. AMBER FF for proteins and nucleic acids
 “specific” FF
 The ability to transfer parameters form one molecule to another is
crucial
 The errors in the FF have to be balanced (similar error on different FF
terms)
 Transferability is helped by using the same parameters for as wide a
range of situations as possible.
 Bonding terms depend solely upon the atom types involved (C hybridization:
sp3,sp2,sp)
 vdW parameters could be independent of the atom type hybridization
3.8 Periodic Boundary Condition

 Computational capabilities are limited
 We only can simulate a small partition of
physical systems
 Surface effect
 Large fraction of molecules can be expected at
the surface rather than in the bulk
 Periodic Boundary Conditions (PBC)
 Eliminates surface effect-edge molecules
 Molecules have a mirror image
 Changes in one box are matched exactly in the
other boxes
 Particle motion in the central box
 Its periodic image in every one of the other boxes
moves with exactly the same orientation in exactly
the same way.
 Molecules exiting one wall re-enter through
the opposite!
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3.8 Periodic Boundary Condition

 Within a system constituted by infinite
images of our simulation box,
 The non bonded energy would become an
infinite summation over an infinite array of
periodic images
 Minimum image convention (MIC)
∆x
 Avoid infinite summation of NBI
 Under PBC, inter-particle distances are
measured using MIC ∆y
 We must ensure rcutoff < L/2 so Lx
particles do not interact with multiple
images of neighbors
∆
∆ ∆
3.9 Truncation of non-bonded terms

 Non bonding potentials are computed as atom pairs
 The absolute number of computed pair energies increases exponentially
with the number of atoms present in the system
 Using PBC this problem becomes much more acute, even
when using MIC
 However, the effective force of the non bonding potentials depends on
the distance
 The interaction rapidly decrease as function of interatomic distance
 More acute in vdW interactions
 We can assume that beyond certain inter particle distance the energy contribution
could be negligible.
 We apply a cut–off distance (both real space or images)

beyond which non bonded pairs are not considered
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3.9.1 Van der Waals Potential

 Cut-Off
 MCI conditions are defined by the cut off distance
 Any particle interacts only with those images that lie within the
boundary marked by the cut off distance
 Shift
 Lennard-Jones decays steadily over whole range and decays smoothly
to zero between user defined distances
 Smoothing function either at the energy or at the force expressions
 Steinbach et al. J. Comput. Chem. 15 (1994) 667-683
V r S r None shifted function

E
1
0
b
r
3.9.1 Van der Waals Potential

 Switch
 Lennard-Jones energy has a normal
behaviour out to a certain distance
 A correction function that forces energy
dropping to zero at cut off distance is
applied
 Steinbach et al. J. Comput. Chem. 15 (1994)
667-683
 Switching function applied to CHARMM
potentials
V r S r
1,
2 3
,
0,
24
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3.9.2 Long-range electrostatic

 A cut-off introduces a
discontinuity in both the
Lennard-Jones
1.5
Coulomb
potential energy and the forces 1.0
E
1 qq
4 rij
near the cut-off value. 0.5
 If the potential energy function non 0.0
decays faster than 1/r3  makes -0.5
potential energy to diverge -1.0

1 2 3 4
 Coulombic interactions must be

treated specially 1
2 | |
 They characteristically extend they ,
effect through very long ranges n = n1 a1 + n2 a2 + n3 a3

 The decay of magnitude is very slow prime indicates omission of terms
with i = j when n = 0
3.9.2.1 Ewald’s Summation

 The Ewald sum splits up the slowly converging sum over the
Coulomb potential into the sum of two rapidly converging
series plus a constant term
 The real (direct) space sum ( ), the reciprocal (imaginary, or

Fourier) sum ( ), and the constant term ( ), known as the self-
term
Physical meaning
Each point charge is surrounded by a charge
distribution of equal magnitude and opposite
sign (Gaussian distribution)
A charge distribution of the same sign as the
original charge, and the same shape is also Toukmaji & Board, Comp. Phys. Comm. 95 (1996) 73-92
added
This cancelling distribution reduces the overall potential to that due to the original set
of charges (summed in reciprocal space)
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3.9.2.1 Ewald’s Summation

 Self Term
 Correction term that cancels out the interaction of each of the introduced artificial
Gaussian counter charges with themselves
 corresponds to the sharp distribution of charge
 nmax, kmax, and κ control the convergence of the sums
 Usually, κ is chosen such that only the (n = 0) term is required to obtain the desired level
of accuracy, namely the minimum image convention within a spherical cutoff (Rc)
| |
1 | |
2 | |
,
| |
2 exp ⁄4
cos
, k = 2πm, and m sums over all integer translations of

the reciprocal lattice m = m1 a1* + m2 a2* + m3 a3*
3.10 Introduction to the GROMACS,

AMBER, and CHARMM Packages
 GROMACS
 GROningen MAchine for
Chemical Simulations
 http://www.gromacs.org/
 Primarily designed for
 Biochemical molecules
 i.e. proteins, lipids and
nucleic acids
 General systems
 i.e. polymers etc.
 Open source
 Serial, MPI and GPU binaries
26
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 AMBER
 Assisted Model Building with Energy
Refinement
 http://ambermd.org/
 Open source (PMEMD under licence)
Solomon-Ferrer et al., WIRE: Comp. Mol. Sci., 3 (2013) 198-210

 CHARMM
 Chemistry at HARvard Macromolecular Mechanics
 http://www.charmm.org/
 Primary focus
 Molecules of biological interest, i.e. peptides, proteins, prosthetic groups, small
molecule ligands, nucleic acids, lipids, and carbohydrates
 Systems in solution, crystals, and membrane environments
 Free for academic users
 Main Features
 Molecular Mechanics & Molecular  Reaction Path Determination
Dynamics
 Solvent and crystal simulations
 Genetic Algorithm
 Umbrella Sampling  Multi-body dynamics (MBOND)
 Miscellaneous Mean Field Potentials
(MMFP)  Quantum and Molecular
 Monte Carlo simulation package Mechanical Force Field (QM/MM)
 Free Energy Perturbation  NMR analysis facility
Calculations
 Normal Mode and Molecular  Reference Interaction Site Model
vibrational analysis facility (RISM)
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Computational Modelling in Physics,

Chemistry and Biochemistry
Molecular Modelling
Unit 3. Classic Model
Juan Torras, Univ. Politècnica Catalunya (2015)
28

MolecularModelling Unit 3 v2

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MolecularModelling Unit 3 v2

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28/10/2015

Computational Modelling in Physics,

Unit 3. Classic Model

Juan Torras, Univ. Politècnica Catalunya (2015)

 is the most important

3.1. Molecular Interactions Modelling

3.1. Molecular Interactions Modelling

 V0 corresponds to the energy minimum, thus can be set to 0, as

3.1. Molecular Interactions Modelling

 which generally remains valid when the displacement form the

3.1. Molecular Interactions Modelling

3.1. Molecular Interactions Modelling

3.1. Molecular Interactions Modelling

3.1. Molecular Interactions Modelling

3.1. Molecular Interactions Modelling

3.1. Molecular Interactions Modelling

Michael Levitt, Nobel Lecture (2013)

3.2 Bond Stretching

 Allow a better approximation to Morse potential

3.3 Angle Bending

3.4 Torsional Terms

3.4 Torsional Terms

 More complicated torsional barriers V2=1.175; n=2; γ=0

3.5 Improper Torsions

3.6 Non-bonded interactions

 Van der Waals interactions

PNAS, cover photography, September 17, 2002; 99 (19)

3.6.1 Electrostatic Interactions

3.6.1.1 Multipole expansion

3.6.1.1 Multipole expansion

3.6.1.1 Multipole expansion

 Efficient to calculate E between molecules

3.6.1.2 Point-charge models

 We assume that if sufficient point charges are used then

3.6.1.3 Charge Derived from the

 (QM potential) ; (Potential from set of points)

3.6.1.3.1 RESP charges

 Potential calculated on 4 shells of surfaces defined by {1.4,

 ESP at each point derived from QM

3.6.1.4 Distributed Multipole Models

 Calculates the multipoles from a quantum

3.6.1.5 Using Charge schemes to study

Hunter & Saunders, JACS 112 (1990) 1024

3.6.2 Van der Waals Interactions

3.6.2.1 Dispersive Interactions

3.6.2.2 Modelling Van der Waals

3.6.3 Molecular Modelling of Hydrogen

3.6.3 Molecular Modelling of Hydrogen

3.7 Force Field Models

3.7.1 All Atom versus United Atom

3.7.2 Force Field Parametrization

3.7.2 Force Field Parametrization

Marrink et al., J. Phys. Chem. B 111 (2007) 7812-7824

Ring particles (2 or 3 to 1 mapping)

3.7.2 Force Field Parametrization

3.8 Periodic Boundary Condition

3.8 Periodic Boundary Condition

3.9 Truncation of non-bonded terms

 We apply a cut–off distance (both real space or images)

3.9.1 Van der Waals Potential

V r S r None shifted function

3.9.1 Van der Waals Potential

3.9.2 Long-range electrostatic