Molecular modeling molecular mechanics
Download
1 / 21

Molecular Modeling: Molecular Mechanics - PowerPoint PPT Presentation


  • 205 Views
  • Uploaded on

Molecular Modeling: Molecular Mechanics. C372 Introduction to Cheminformatics II Kelsey Forsythe. Guidelines for Use. What systems were used to parameterize How is energy calculated What assumptions are used in the force field How has it performed in the past. Transferability.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' Molecular Modeling: Molecular Mechanics' - odette


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
Molecular modeling molecular mechanics

Molecular Modeling:Molecular Mechanics

C372

Introduction to Cheminformatics II

Kelsey Forsythe


Guidelines for use
Guidelines for Use

  • What systems were used to parameterize

  • How is energy calculated

  • What assumptions are used in the force field

  • How has it performed in the past


Transferability
Transferability

  • AMBER (Assisted Model Building Energy Refinement)

    • Specific to proteins and nucleic acids

  • CHARMM (Chemistry at Harvard Macromolecular Mechanics)

    • Specific to proteins and nucleic acids

    • Widely used to model solvent effects

    • Molecular dynamics integrator


Transferability1
Transferability

  • MM? – (Allinger et. al.)

    • Organic molecules

  • MMFF (Merck Molecular Force Field)

    • Organic molecules

    • Molecular Dynamics

  • Tripos/SYBYL

    • Organic and bio-organic molecules


Transferability2
Transferability

  • UFF (Universal Force Field)

    • Parameters for all elements

    • Inorganic systems

  • YETI

    • Parameterized to model non-bonded interactions

    • Docking (AmberYETI)


How is energy calculated
How is Energy Calculated

  • Valence Terms

  • Cross Terms

  • Non-bonding Terms

    • Induced Dipole-Induced Dipole

    • Electrostatic/Ionic (Permanent Dipole) System not far from equilibrium geometry (harmonic)

  • Energy is ?

    • Strain Energy (E=0 at equilibrium bond length/angle)

    • Field Energy (Energy due to Non-bonding terms)

    • Atomistic Heats of Formation (Parameterized so as to yield chemically meaningful values for thermodynamics)

      • K. Gilbert: This is only in the MM?-type force fields


Assumptions
Assumptions

  • Hydrogens often not explicitly included (intrinsic hydrogen methods)

    • “Methyl carbon” equated with 1 C and 3 Hs

  • System not far from equilibrium geometry (harmonic)

  • Solvent is vacuum or simple dielectric



Modeling potential energy1

0

0 at minimum

Modeling Potential energy


Assumptions harmonic approximation
Assumptions:Harmonic Approximation


Assumptions harmonic approximation1
Assumptions:Harmonic Approximation

Determining k?


Assumptions harmonic approximation2
Assumptions:Harmonic Approximation

E(.65)=3.22E-20J

E(.83)=2.13E-20J

Dx=.091


Assumptions harmonic approximation3
Assumptions:Harmonic Approximation


Assumptions harmonic approximation4
Assumptions:Harmonic Approximation


Assumptions1
Assumptions

  • Hydrogens often not explicitly included (intrinsic hydrogen methods)

    • “Methyl carbon” equated with 1 C and 3 Hs

  • System not far from equilibrium geometry (harmonic)

  • Solvent is vacuum or simple dielectric


Assumptions solvent effects
Assumptions:solvent effects

DFT

H2 in Pd

Christensen, O. B. et. al, Phys. Rev. B. 40, 1993 (1989)


Intermolecular atomic models
Intermolecular/atomic models

  • General form:

  • Lennard-Jones

Van derWaals repulsion

London Attraction


Mmff energy
MMFF Energy

  • Electrostatics (ionic compounds)

    • D – Dielectric Constant

    • d - electrostatic buffering constant


Mmff energy1
MMFF Energy

  • Analogous to Lennard-Jones 6-12 potential

    • London Dispersion Forces

    • Van der Waals Repulsions

The form for the repulsive part has no physical basis and is for computational convenience when working with largemacromolecules. K. Gilbert: Force fields like MM2 which is used for smaller organic systems will use a Buckingham potential (or expontential) which accurately reflects the

chemistry/physics.


Pros and cons

N >> 1000 atoms

Easily constructed

Accuracy

Not robust enough to describe subtle chemical effects

Hydrophobicity

Excited States

Radicals

Does not reproduce quantal nature

Pros and Cons


Caveats
Caveats

  • Compare energy differences NOT energies

  • Always compare results with higher order theory (ab initio) and/or experiments


ad