Computational Chemistry
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Transcript of Computational Chemistry
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Computational Chemistry
Molecular Modeling
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Molecular Modeling Requires mastering a broad range of fields
Chemistry, Physics, Mathematics, Computer science, Biology, Pharmacology, serendipity
Molecular Modeling is the generation, manipulation and representation of three dimensional structures of molecules and associated physicochemical properties.
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What is Molecular Modeling? Term used to describe computer based
methods which give both quantitative and qualitative insight into the way molecules interact and react.
Within this definition are many possible methods Empirical Quantum Dynamics
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History - Big Picture Handheld molecular models
Think organic chemistry Pauling discovery helix & sheets Watson & Crick discovery DNA
X-ray crystal structures (experimental) Computer graphics
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More Specifically3 Dimensional structures of molecules and
associated physicochemical properties Generation Manipulation Representation
Four Stages Structure building Structure analysis Structure comparison Structure prediction
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How should a molecule be represented? Theory H = E Chemical formula C14H20N2O2 2D structure
Models Computer graphics
Black and white line representation, color line drawing, color ball and stick model, space filling model, Van der Waals dot surface, wire surface, electrostatic potential energy surface
NH
O NH
OH
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Computer Graphics
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Relationship to ExperimentExperiment Computation
Define Problem
Design experimental specify and buildprocedure and setup modelsapparatus
Do experiment Do calculationAnalyze Results
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Computational Approaches Quantum chemical
Ab initio Semi empirical Density functional theory
Molecular Mechanics Force field calculations Requires use of the Born-Oppenheimer
Theorem Electrons move in stationary field of the nuclei;
electronic and nuclear motion are separable
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Quantum Theory Solving Schrodinger wave equation to minimize
the electronic energy of the system Fundamental Equation Ĥ = E = wave function of system (eigenfunction) Ĥ = Hamiltonian operator E = energy eigenvalue Each wave function (that is a solution to the
Schrodinger equation) must meet certain mathematical restrictions and corresponds to a different stationary point of the system. The stationary point with the lowest energy eigenvalue is the ground state of the system.
VERY HARD TO DO!!!
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Hartree Fock Theory Using MO theory, define simplified wave functions
(Hartree-Fock wave functions) which can be further broken down into a linear combination of one-electron atomic orbitals (LCAO-MO).
Choice of atomic orbitals is important since they define the basis set (gaussian type orbitals)
Take a linear combination of gaussian orbitals to define electron conditions. (Noble Prize to John Pople 1998)
Use Self Consistent Field Method to calculate total electronic Energy
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Limitations of Hartree Fock Use of simplified wave function Single assignment of electrons to orbitals
Need to expand on the configuration interaction of electrons
Other ab initio methods Moller-Plesset Perturbation Theory
Typically terminated at the second order MP2, MP4
Coupled Cluster Theory
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Semi-Empirical Methods Use simplifying assumptions to solve the
energy and wave function of molecular systems.
Use simpler Hamiltonian operator Use empirical parameters for some of
the two-electron integrals Complete or partial neglect of other
electron integrals
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Semi-Empirical Methods
CNDO – Complete Neglect of Differential Overlap Bonding not calculated
MINDO – Modified Intermediate Neglect of Differential Overlap
MNDO – Modified Neglect of Differential Overlap Fix is AM1 method
Allow for faster calculations Allow for bigger chemical systems Obvious problems with accuracy
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Density Functional Theory Replace complicated multi-electron
wave function and the Schrodinger equation with simpler equation for calculation of electron density of the molecular system.
Local density approximation where electronic properties are determined as functions of the electron density through the use of local relationships.
Nobel Prize to Walter Kohn in 1998
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DFT One to one correspondence between
ground state wave function and ground state electron density
Simpler to calculate G. S. electronic wave function from G. S. electronic density
Faster and greater Accuracy than conventional ab initio
Problematic with excited state systems Newest method – not standardized
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Molecular Mechanics Based on Born-Oppenheimer Approximation
Electrons move in stationary field of the nuclei; electronic and nuclear motion are separable
Calculating position of nuclei only Through set of simple equations called a force field
Uses the notion that molecules have “natural” bond lengths and bond angles Molecules will adjust their nuclear positions to take up
these natural values In a strained system, the molecule will deform in
predictable ways to minimize the strain (and allow for the strain energy of the molecule to be calculated.)
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Molecular Mechanics Classical mechanics approach
Develop a set of potential functions called the force field which contains adjustable parameters that are optimized to obtain the best match to the experimental properties.
Mathematical approach in an attempt to reproduce molecular structures, potential energies and other features
Etotal= Es + Eb + Etor + Evdw + Eele + ….
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Molecular Mechanics Programs Amber Charmm Discover MM2 MM3 MM4 Tripos
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Limitations of Molecular Mechanics
Parameters for a particular class of compounds must be in the program
Parameters and equations must be accurate Extrapolation to “new” molecular structures
may be dangerous Does not deal with electrons
FOR ALL METHODS Local minimum problem Over interpreting results – looking at
individual components
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Applications of Molecular Modeling Understanding Mechanisms Understanding Conformations Understanding Biological Activity Understanding the Pharmacophore Understanding Protein Structures
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Computational Battle What is the goal of the project?
Small vs. Large molecular systems Accuracy vs speed