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Molecular Modeling Workshop
Molecular Modeling
Workshop
Laboratory for Molecular Simulation (LMS)
Manager: Dr. Lisa M. Pérez
Director: Prof. Michael B. Hall
lms.chem.tamu.edu
[email protected]
Office: Rm. 2109 Chemistry (CHAN)
phone: 845-9384
Please turn your cell phones to silent for the lecture
April 10, 2015
Introduction to Molecular Modeling
—  Visualization
—  Computational Chemistry
—  Quantum Mechanics
—  Ab initio
—  Density-Functional Theory
—  Semi-Empirical
—  Classical Mechanics
—  molecular mechanic MM
—  molecular dynamics MD
—  Monte Carlo
Molecular Modeling
Visualization
Computational
Chemistry
Information
Science
—  Prediction of properties
—  Structural, chemical, physical, biological, etc.
—  Understand, explain, and possibly predict chemical processes
—  Tools to gain insight at the atomic and molecular level
—  Microscopic ⇔ Macroscopic
April 10, 2015
Laboratory for Molecular Simulation, Texas A&M University
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Molecular Modeling Workshop
Microscopic ó Macroscopic
Time
Grids
>min
Continuum
(FEA, CFD)
Segments
s
Mesoscale
µs
Atoms
ns
Electrons
ps
fs
Quantum
Mechanics
HΨ=EΨ
Molecular
Dynamics
F=ma
Ångstroms
nm
µm
mm
m
Distance
April 10, 2015
Visualization
—  Building
—  Draw in 2-D
—  Convert to 3-D
—  Rotate
—  Rendering
—  Line
—  Stick
—  Ball and Stick
—  CPK Ball
—  Cartoon
Maynard, D. and Vigh, G.
Dept. of Chemistry, Texas A&M University
—  Surfaces
—  Visualizing crystal structures
April 10, 2015
Laboratory for Molecular Simulation, Texas A&M University
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Molecular Modeling Workshop
Visualization
Image generated in Chimera
April 10, 2015
Software Purchases
—  The Laboratory for Molecular Simulation currently provides
a wide variety of academic licenses for commercial and
academic molecular modeling software for students and
researchers at Texas A&M University.
—  The LMS assists in the purchase of software that we currently
do not provide. $$$
—  The LMS also provides support in the use of Molecular
Modeling software through administration (ie. installation
and updates), training, and scripting.
April 10, 2015
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Molecular Modeling Workshop
Software – Quantum Mechanics
Name
Description
Licensing
Price
ADF
Quantum Mechanics (QM)
8 CPU Floating License
$$
ABINIT
QM (Molecular and Periodic Systems)
Site License*
Free
AMPAC
QM (Semi-empirical)
Site License
$
CRYSTAL
QM for Periodic Systems
Site License
$
Dalton
QM Specializing in magnetic/electric properties
Site License*
Free
Discovery Studio
QM & MM/MD suite of software with a user-friendly
Interface for Life Sciences
Floating Licenses
$$$
GAMESS-US
QM
Site License*
Free
Gaussian
QM
Site License
$
Materials Studio
MM/MD & QM suite of software with a user-friendly
GUI for Materials Sciences
Floating Licenses
$$$
MOLPRO
QM (specializing in high-level calculations)
Group Licenses
$$
NWChem
QM
Site License*
Free
ORCASIESTA
QM specializing in spectroscopic properties
Site License*
Free
SIESTA
QM specializing in electron transport and Solids
Site License*
Free
VASP
QM specializing in QMD and ultra-soft ECPs
24 Restricted Licenses
$$
* Users need to register with the software provider at no charge.
April 10, 2015
Software – Molecular Mechanics/Dynamics
Name
Description
Licensing
Price
AMBER
Molecular Mechanics/Dynamics (MM/MD)
Site License
$
CHARMm
MM/MD
8 Floating Licenses
$$/$
Discovery Studio
MM/MD & QM suite of software with a user-friendly
GUI for Life Sciences
Floating Licenses
$$$
GROMACS
MM/MD specializing in speed and coarse-grained
simulations
Site License*
Free
GROMOS
MM/MD
Group License
$
LAMMPS
MM/MD
Site License*
Free
Materials Studio
MM/MD & QM suite of software with a user-friendly
GUI for Materials Sciences
Floating Licenses
$$$
MOE
MM/MD – Drug discovery software
Floating Licenses
$$$
ICM
MM/MD and more
Floating or Node locked
Licenses§
Free &
$$$
Schrödinger
MM/MD and more
Floating Licenses
$$$
NAMD
MM/MD
Site License*
Free
* Users
§ LMS
need to register with the software provider at no charge.
does not currently hold a license
Laboratory for Molecular Simulation, Texas A&M University
April 10, 2015
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Molecular Modeling Workshop
Software – Graphical User Interfaces (GUI)
Name
Description
Licensing
Price
AIM2000
Wavefunction Analysis (Bader Analysis)
LMS License
$
AGUI (Gaussview)
GUI for AMPAC and Gaussian
Site License
$
AOMix
MO analysis & spectra simulation
Site License
$
Avogadro
Visualizer and GUI for many QM and MM codes
Site License*
Free
Chemmisian
GUI for the analysis of electronic structure and spectra.
Site License*
$
Chimera
Interactive Visualization and analysis of Molecular
Structures
Site License*
Free
Gabedit
GUI for computational chemistry software
Site License*
Free
gOpenMol
GUI for computational chemistry software
Site License*
Free
Jimp2
GUI for Fenske-Hall (QM) and more
Site License*
Free
Maestro
GUI for Schrödinger Suite of Software
Token Based Licnese
$$$
Molden
GUI to visualize results of modeling software
Site License*
Free
VMD
GUI for NAMD and more
Site License*
Free
* Users need to register with the software provider at no charge.
April 10, 2015
Materials Studio by Accelrys
Bundle Name
# of Licenses
Materials Studio
Base
25
Visualizer
Conformers
Forcite Plus Parallel
Gaussian Interface
QSAR+
Modules Included in Bundle
MS Pipeline Pilot Collection
Reflex
VAMP Parallel
VAMP Interface
Materials Studio
Classical &
Mesoscale
1
Adsorption Locator
Amorphous Cell
Blends
COMPASS Parallel
GULP Parallel
GULP Interface
Mesocite
Mesodyn
Mesodyn Interface
Sorption
Synthia
Materials Studio
Quantum
3
CASTEP Parallel
CASTEP Interface
DFTB+ Parallel
DMOL3 Solid State Parallel
DMOL3 Solid State Interface
GULP Parallel
GULP Interface
NMR CASTEP Parallel
ONETEP
QMERA
QMERA Interface
1
Equilibria
April 10, 2015
Laboratory for Molecular Simulation, Texas A&M University
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Molecular Modeling Workshop
Discovery Studio by Accelrys
Bundle Name
# of Licenses
Modules Included in Bundle
Discovery Studio
Base
18
Visualizer
Analysis
Biopolymer
Catalyst Conformation
Catalyst Score
CDOCKER
CHARMm
DMOL3 Molecular
MMFF (Force-Field)
Protein Refine
QUANTUMm (QM/MM)
Discovery Studio
Structure Based
Design
2
Catalyst DB Build
Catalyst DB Search
Catalyst Hypothesis
Catalyst SBP
Catalyst Shape
CFF
De Novo Evolution
De Novo Ligand Builder
Flexible Docking
Libdock
LigandFit
LigandScore
LUDI
MCSS
Discovery Studio
Protein
3
Modeler
Protein Families
Protein Health
Protein Docking
Sequence Analysis
X-ray analysis (CNX)
April 10, 2015
Schrödinger
Units
Items
15 Tokens
Glide (5 Tokens)
QikProp (2 Tokens)
Liaison (4 Tokens)
Canvas (1 Token)
Strike (1 Token)
LigPrep (1 Token)
10 Licenses
BioLuminate GUI
10 Tokens
QSite (4 Tokens)
pKa Predictor (3 Tokens)
MacroModel (2 Tokens)
Epik (1 Token)
ConfGen (3 Tokens)
SiteMap (1 Token)
Jaguar (2 Tokens)
1 License
PIPER
April 10, 2015
Laboratory for Molecular Simulation, Texas A&M University
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Molecular Modeling Workshop
MOE – Molecular Operating
Environment by Chemical Computing
Group
LMS has a
3 Token License
With an option for
Many teaching license at no charge.
April 10, 2015
Computational Chemistry
—  Quantum Mechanics
—  Ab initio - based on first principles
—  Hartree-Fock Theory (HF)
—  Møller-Plesset Perturbation Theory (MPn ; n = 2, 3, 4, … )
—  Configuration Interaction (CI ; CIS, CISD, CISDT, … )
—  Coupled-Cluster (CC ; CCD, CCSD, CCSD(T), CCSD(TQ), … )
—  Complete Active Space Self Consitent Field (CASSCF)
—  Multi-Reference Configuration Interaction (MRCI)
—  and many more
—  Density Functional Theory
—  B3LYP, BP86, B3PW91, mPW1PW91, PBE, M06, TPSS
—  and many more
—  Semi-empirical
—  AM1
—  PM3
—  PM5
—  and many more
April 10, 2015
Laboratory for Molecular Simulation, Texas A&M University
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Molecular Modeling Workshop
Quantum Mechanics
—  Ab initio methods
—  Schrödinger Equation
—  HΨ=EΨ ; time-independent Schrödinger equation.
—  Applicable to any system, in principle.
—  Can model bond breaking and formation
—  Used for benchmark values
—  Can only be used for small system ( normally < 200 atoms )
—  Computationally expensive
—  Scaling: Nn n=2, 3, 4, 5, 6, …
—  Commonly used codes
—  Gaussian 09, GAMESS-US, Spartan, NWChem
—  Q-Chem, MOLPRO, Dalton, GAMESS-UK, CRYSTAL
—  and many more
April 10, 2015
Quantum Mechanics
—  Density Functional Theory (DFT)
—  Total energy of a system depends only on the electron density
Etot= F[ρ(x,y,z,s)]
—  Applicable to any system, in principle.
—  Can model bond breaking and formation
—  Includes electron correlation with little cost compared to ab initio
methods
—  Exact functional is not known
—  Commonly used software for DFT
—  Gaussian 09, Jaguar, DMol3, Turbomole, Amsterdam Density Functional
(ADF), GAMESS-US, NWChem, MOLPRO, Spartan, GAMESS-UK,
CRYSTAL, and many more
April 10, 2015
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Molecular Modeling Workshop
Reaction Mechanism Calculations
Cunxiang Zhao, T. Andrew Mitchell, Ravikrishna Vallakati, Lisa M. Pérez, and Daniel Romo
J. Am. Chem. Soc., 2012, 134 (6), pp 3084–3094
DOI: 10.1021/ja209163w
April 10, 2015
Reaction Mechanism Calculations
April 10, 2015
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Molecular Modeling Workshop
Reaction Mechanism Calculations
April 10, 2015
3 + 6Acetonitrile ➛ 4 + 3Acetonitrile ➛ 5 + Naphthalene
2+
Ru
3
c2v
Ru
2+
5
c2v
Ru
N
N
N
Ru
N
N
N
2+
Ru
4
cs
Ru
N
N
N
April 10, 2015
Laboratory for Molecular Simulation, Texas A&M University
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Molecular Modeling Workshop
3 + 6Acetonitrile ➛ 4 + 3Acetonitrile ➛ 5 + Naphthalene
2+
2+
Ru
4
cs
Ru
N
N
Ru
3
c2v
N
Ru
2+
5
c2v
Ru
N
N
Ru
N
N
N
N
April 10, 2015
Quantum Mechanics – (ab initio, DFT, Semi-empirical)
Reaction Path Calculations
Thomson (Pérez), L.M.; Hall, M.B. J. Am. Chem. Soc.2001, 123, 3995.
•  Calculating transition states is significantly more difficult than
minima.
•  Experimental data is needed to narrow reaction path possibilities to
be investigated computationally.
April 10, 2015
Laboratory for Molecular Simulation, Texas A&M University
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Molecular Modeling Workshop
NMR Calculations
Original
assignment for
spectra a)
Upfield
Downfield
(E)-2a is
lower in
energy than
(E)-2a-ZnCl2
April 10, 2015
UV/Vis spectra via TD-DFT
Experimental
TD-DFT
April 10, 2015
Laboratory for Molecular Simulation, Texas A&M University
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Molecular Modeling Workshop
UV/Vis spectra via TD-DFT
Experimental
TD-DFT
April 10, 2015
Wavefunction Analysis
Atoms in Molecules (AIM)
A) Contour plot of the electron density of [1-F]+ showing the short and long C-F bonds. The
plane was selected to contain the C02, F, and C01 atoms. B) Contour plot of –1/4∇ 2 ρ(r) for
[1-F]+ illustrating the covalent nature of the short C-F bond and the dative nature of the long
C-F bond. Positive and negative values are shown with blue solid and red dashed lines,
respectively.
April 10, 2015
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Molecular Modeling Workshop
Quantum Mechanics
—  Semi-empirical Methods
—  AM1, PM3, PM5, PM7, PM7-TM, SAM1, etc.
—  Approximate solution to the Schrödinger equation
—  Replaces the expensive integrals with parameters
—  Applicability is limited by available parameterization
—  Mostly used for 1st row main group elements
—  Limited applicability to transition metals
—  Can model bond breaking/formation
—  Can model much larger systems than ab initio or DFT
—  Commonly used software
—  MOPAC 2012, Gaussian 09, Chem3d, AMPAC, VAMP, and many
more
April 10, 2015
Molecular Mechanics
—  Newtons equations
—  The potential is approximated by an empirical function
force field that is fitted to approximately reproduce
known interactions
—  Applicability is limited by the availability of
parameterization
—  Generally, the connectivity of atoms cannot change during
the simulation
—  Generally, not suitable for reaction mechanisms
—  Can predict relative energies of different conformational states of
material
—  And much more
April 10, 2015
Laboratory for Molecular Simulation, Texas A&M University
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Molecular Modeling Workshop
Molecular Mechanics
—  The molecule is considered to be a collection of atoms held
together by simple elastic or harmonic forces.
—  Force Field - A mathematical expression that describes the
dependence of the energy of a molecule on the coordinates of the
atoms in the molecule.
—  Force Field Energy Expression:
— 
E = Ebond + Eangle + Etorsion + Eoop(out-of-plane) + Enon-bond + Eother
April 10, 2015
Force Field Terms
Bond & Angle
Terms
April 10, 2015
Laboratory for Molecular Simulation, Texas A&M University
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Molecular Modeling Workshop
Force Field
Terms - Torsion,
Inversion &
Coulombic
Terms
April 10, 2015
Force
Field
Terms –
Van der
Waals
Terms
April 10, 2015
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Molecular Modeling Workshop
Force Field
Terms –
Cross Terms
April 10, 2015
Class II
forcefield
(CFF91)
Bond stretching
Angle bending
Torsion
Out-of-plane
5-11 Cross Terms
Coulombic
Laboratory for Molecular Simulation, Texas A&M University
Van der Waals
April 10, 2015
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Molecular Modeling Workshop
Molecular Mechanics
—  Force Fields differ in their parameters, cross terms and the
method of development
—  Class I - simple functional form with data fitted to quantum
mechanical calculations and/or experiment
—  Class II - more complicated functional form using cross terms and
data fitted to quantum mechanical calculations and/or experiment
—  Class III - new generation force fields that incorporate polarizability
—  Rules Based - covers most of the periodic table
—  Fundamental quantities are derived for each atom type: electronegativity,
hardness, atomic radius, etc.
—  Forcefield parameters are derived at runtime using a series of theoretically or
empirically derived rules
—  Specialist - developed for a particular family of compounds
flourinated polymers, zeolites, etc.
April 10, 2015
Common Force Fields
—  MM2/MM3/MM4: Molecular Mechanic Force field for
small organic molecules
—  CHARMM: Chemistry at Harvard Macromolecular
Mechanics
—  AMBER: Assisted Model Building with Energy Refinement
—  OPLS: Optimized Parameters for Liquid Simulation
—  CFF: Consistent Force Field
—  CVFF: Valence Consistent Force Field
—  MMFF94: Merck Molecular Force Field 94
—  DREIDING: Generic rules based force field
—  UFF: Universal Force Field
—  ReaxFF: Speciality force-field to allow bond breaking
April 10, 2015
Laboratory for Molecular Simulation, Texas A&M University
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Molecular Modeling Workshop
UFF – Universal Force-Field
—  The Universal forcefield's atom types are denoted by an element name of one or two
characters followed by up to three other characters:
—  The first two characters are the element symbol (i.e., N_ for nitrogen ).
—  The third character (if present) represents the hybridization state
—  1 = linear
—  2 = trigonal
—  R = an atom involved in resonance
—  3 = tetrahedral
—  4 = square planar
—  5 = trigonal bipyramidal
—  6 = octahedral
—  The fourth and fifth characters (if present) indicate characteristics such as
—  the oxidation state (i.e., Rh6+3 represents octahedral Rh in the +3 formal oxidation
state
—  H___b indicates a diborane bridging hydrogen type
—  O_3_z is a framework oxygen type suitable for zeolites).
A. K. Rappe; C. J. Casewit; K. S. Colwell; W. A. Goddard III; W. M. Skiff J. Am. Chem. Soc. 114, 10024-10035
(1992).
April 10, 2015
Force Field Atom Types
CFF/ CFF91/ PCFF
carbonyl functional groups C and O
c_0 carbonyl carbon of aldehydes, ketones
c_1 carbonyl carbon of acid, ester, amide
c_2 carbonyl carbon of carbamate, urea
cz carbonyl carbon of carbonate
o= oxygen double bonded to O, C, S, N, P
o_1 oxygen in carbonyl group
o_2 ester oxygen
oo oxygen in carbonyl group, carbonate only
oz ester oxygen in carbonate
April 10, 2015
Laboratory for Molecular Simulation, Texas A&M University
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Molecular Modeling Workshop
Atom Types
o=
hn
Sf
Cp
nb
s1
PCFF force field - PCFF was developed based on CFF91 and is intended for
application to polymers and organic materials. It is useful for polycarbonates, melamine
resins, polysaccharides, other polymers, organic and inorganic materials, about 20
inorganic metals, as well as for carbohydrates, lipids, and nucleic acids and also cohesive
energies, mechanical properties, compressibility's, heat capacities, elastic constants. It
handles electron delocalization in aromatic rings by means of a charge library rather than
bond increments.
April 10, 2015
Minimization
—  Minimize the potential energy
Energy
E = Ebond + Eangle + Etorsion + Eoop + Enonbond + Eother
Local
Minima
Local
Minima
Global
Minimum
Local
Minima
April 10, 2015
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Molecular Modeling Workshop
Minimization Strategies
—  Cascade Approach - Smart Minimizer
—  Steepest decent
—  Max gradient > 100
—  Conjugate Gradient
—  Max gradient < 100
—  Newton
—  iterative (pure) Newton-Raphson.
—  BFGS (Broyden-Fletcher-Goldfarb-Shanno)
—  DFP (Davidon-Fletcher-Powell)
—  truncated Newton-Raphson
—  Final Convergence
—  Many software programs will perform these steps for you,
but some programs you will need to perform this manually.
April 10, 2015
Mutations and Minimization
Native
April 10, 2015
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Molecular Modeling Workshop
Molecular Dynamics
—  Minimization methods will only optimize your molecule to
the closest local minimum
—  Methods to find the global minimum
—  Systematic conformational search
—  Very time consuming and essentially impossible for anything but the
smallest of molecules
—  CH3(CH2)n+1CH3
—  n=1
3 possible configurations
<1 sec
—  n=2
243
1 min
—  n=10
59,049
2 hour
—  n=15 14,348,907
100 days
—  Molecular Dynamics, Random Sampling, Monte Carlo, Hybrid
Monte Carlo/Dynamics methods
—  Samples the potential energy surface by perturbing the geometry
April 10, 2015
Molecular Dynamics
—  Methods to find the global minimum
—  High temperature dynamics
—  Simulated annealing
—  Quench dynamics
Energy
T(K)
Energy supplied to the minimized
structure at the start of the simulation
minimize
Time ps
Simulated Annealing
Time ps
Quench Dynamics
April 10, 2015
Laboratory for Molecular Simulation, Texas A&M University
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Molecular Modeling Workshop
Molecular Dynamics
—  Molecular Dynamics Variations
—  Constant Volume - Constant Temperature (NVT)
—  Constant Volume - Constant Energy (NVE)
—  Constant Pressure – Constant Temperature (NPT)
—  construct a set of velocities based on the ensemble being used
—  Velocities satisfy the Maxwell-Boltzmann distribution
—  Each run will start with a different random seed
—  Allow atoms to move for one time step
—  Calculate the force on the atoms - forcefield
—  Calculate the acceleration F=ma
—  Calculate the new velocity
—  Calculate the new position
1
r (t + δ t ) = r (t )+ δ t v(t )+ δ t 2 a (t )
2
1
v(t + δ t ) = v(t )+ δ t (a (t )+ a(t + δ t ))
2
1
r (t + δ t ) = r (t )+ δ t v(t )+ δ t 2 a (t )
2
—  Repeat for as many time steps as desired
April 10, 2015
Molecular Dynamics
—  Choosing a time step
—  Your time step should be a factor of 10 smaller that the fastest process
in your system.
—  Molecular motions such as rotations and vibrations are on the order of 10-11 -
10-14 s
—  Therefore, a time step of 1 fs (10-15 s) or less must be used for most
systems.
—  You can increase your time step by restricting the fastest processes
—  SHAKE or RATTLE algorithms restrict the vibrational motion of the
molecule of interest
—  Therefore, a time step of 2-3 fs can be used with the SHAKE or RATTLE
algorithm
—  There are some modified shake algorithms that claim they are stable up to
time steps of 8 fs
—  Most simulations are on the order of picoseconds (10-12 s) or
nanoseconds (10-9 s)
—  Protein folding tripzip2 (12-residue protein) folds on the order of
2.5 µs (10-6 s)
April 10, 2015
Laboratory for Molecular Simulation, Texas A&M University
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Molecular Modeling Workshop
Molecular Simulation of ab Initio Protein Folding
for a Millisecond Folder NTL9(1−39)
—  Vincent A. Voelz, Gregory R. Bowman, Kyle Beauchamp, Vijay S. Pande Journal of the
American Chemical Society 2010 132 (5), 1526-1528
—  http://folding.stanford.edu/English/Papers#ntoc6
—  Gromacs(GPU version) and Folding@Home were used for the simulations with implicit
solvation
http://youtu.be/gFcp2Xpd29I
April 10, 2015
Conformational Searches
Ion mobility-mass spectrometry
peptide map of bovine
hemoglobin. Two low-energy
MD calculated structures are
assigned to peptide signals within
the plot: (1) LLGNVLVVVLAR
and (2) LLVVYPWTQR. The
two peptide projections shown
are 15 (top) and 10 Å (bottom).
Brandon T. Ruotolo, Guido F. Verbeck, Lisa M.
Pérez (Thomson), Kent J. Gillig, and David H.
Russell J. Am. Chem. Soc., 124, 4214, 2002.
Ion mobility-mass
spectrometry peptide map of
horse heart myoglobin. Two
low-energy MD calculated
structures are assignaed to
peptide signals within the plot:
(1) HGTVVLTALGGILK and
(2) VEADIAGHGQEVLIR.
The two peptide projections
shown are 10 (top) and 15 Å
(bottom).
April 10, 2015
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Molecular Modeling Workshop
Monte Carlo – RIS Metropolis Monte Carlo
—  In outline, an RMMC simulation proceeds as follows:
—  Perform an energy minimization on the molecule
—  Randomly select a rotatable backbone bond.
—  Select a random torsion value for this bond between -180 and
+180 degrees.
—  Rotate the bond to its new torsion value and compute the new
energy of the chain.
—  Generate a random number, R, between 0 and 1. If
exp[-(Enew -Eold)/kT] > R, keep the new torsion value. Otherwise,
restore the old value.
—  Repeat until the desired number of iterations has been
performed
April 10, 2015
Molecular Dynamics Steps
—  Prepare the Molecule
—  Minimization
—  Required!!!!!!
—  Heating
—  Raise the temperature of the system from 0oC to the desired
temperature.
—  Many programs/researchers skip this step
—  Equilibration
—  Ensure that the system is stable (NVE)
—  Production
—  Run simulation to collect pertinent data
—  NVT, NVE, NPT, etc
April 10, 2015
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Molecular Modeling Workshop
Solvation
—  Explicit Solvation
—  Very expensive
—  Solvent molecules tend to boil off
Non-Periodic water simulation
—  Need to use a periodic system to prevent loss of solvent
molecules
Periodic water simulation
—  Solvent Dielectric Models
—  Treat the solvent as a bulk property
—  Vacuum ε = 1.0
—  Water ε = 78.39
—  Proteins ε = 4.0
—  Constant dielectric constant
—  Distance Dependent Dielectric Models
—  Dielectric constant varies with the distance between the charged
species
—  Generally used for large systems and proteins
April 10, 2015
Informatics
—  Storage and retrieval of information
—  Databases
—  Structures
—  Properties
—  Activities
—  Combinatorial Chemistry
—  Protein Bioinformatics
—  Drug Design
—  Catalysis
—  QSAR – Quantitative Structure Activity Relationships
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Molecular Modeling Workshop
Quantitative Structure Activity Relationship (QSAR)
—  Multi-variant mathematical relationship between a set of
physico-chemical properties (descriptors) and a property of
interest
—  Biological activity
—  Solubility
—  Mechanical behavior
April 10, 2015
Homology
—  Utilizes structure and sequence similarities for predicting unknown
protein structures.
—  Database comparison
—  Molecular mechanics/
dynamics
—  NMR constraints
—  Web resource: http://zhanglab.ccmb.med.umich.edu/I-TASSER/
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Molecular Modeling Workshop
Drug Design
—  Generate a pharmacophore based on a set of known
biologically active molecules.
—  Use the pharmacophore to search a database for other
potentially active molecules.
April 10, 2015
Drug Design
—  de Novo drug design – analog based drug design
—  Design ligands to interact with a know receptor
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Molecular Modeling Workshop
Useful Web Sites
—  Laboratory for Molecular Simulation
—  http://lms.chem.tamu.edu/
—  Listing of Hardware and Software available through the LMS
—  Accelrys Inc.
—  http://www.accelrys.com/
—  Chemical Computing Group, Inc.
—  http://www.chemcomp.com/software.htm
—  MOE – Molecular Operating Environment
—  Schrödinger Inc.
—  http://www.schrodinger.com/
—  http://www.schrodinger.com/supporttraining/18/
—  Support videos
—  Tripos, Inc.
—  http://www.tripos.com/
—  SYBYL software
—  Gaussian, Inc.
—  http://www.gaussian.com/
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