Different Concepts of Molecular Structure

• Experimental Structures versus Classical and Quantum Mechanical Models
• How positions of atoms depend on experimental approach and why?
• Describe the concept of atom type
• Difference between cartesian and internal coordinates
• Given the following (or similar) internal coordinated (Z-matrix)

  1 H 0.000
  2 C 1.100 1
  3 H 1.100 2 120.0 3
  4 O 1.200 2 120.0 3 180.0 4
  

  • Draw a rough sketch of the molecule.
  • What is the name of this molecule.
• What distinquishes PDB Atom names (CA, CB, CG, etc.) from molecular mechanics atom types (e.g. C1, CT, C2, etc.)

Size Matters

• Describe or Define Solvent Accessible Surface
• Describe or Define Molecular Surface
• Describe or Define van der Waals surface
• For a given molecule which of these would have the largest...
  • surface area?
  • volume?
• For a given molecule which of these would have the smallest...
  • surface area?
  • volume?
• Are any of these a trick question (if so, why?)?
• Which surfaces can be calculated with Connolly's MS program?
• Describe how a solvation free energy calculation depends on atom size.

Inter- and Intra-molecular Forces

• Which intermolecular force has "the longest reach"?
• Which are directional (not symmetrical in space with a fixed separation distance)?
• What is the primary reason why the 1/r¹² repulsion term of the typical Lennard-Jones potential is 12th power?
• Be able to argue that the H-bond is a special interaction.
• What are the parameters of the Morse potential function?

Molecular Mechanics

• Know (memorize) one example each of a...
  • harmonic potential
  • torsion potential
  • Coulombic potential
• Be able to recognize the differences between...
  • Lennard-Jones, Hill and Buffered 14-7 potentials
  • Combination rules for minimum energy distances versus contact distances
  • Harmonic, cubic and Morse potential
• What does "Buffered" mean in the Halgren Buffered Coulombic potential?
  • What does such buffering prevent?
• What are two ways to hold a planar geometry at an sp2 carbon center?
  • What argument favors one over the other?
• Be able to draw a rough potential map (energy versus angle) for a typical out-of-plane torsion
• What are critical features of a H-bond potential and what force fields have implemented the various features?
• Bonding potentials are often represented by harmonic functions where as non-bonded potentials which have roughly the same shape are not. Why not?

Uses of a Molecular Mechanics Force Field

• What are the three component groups of a parameter set?
• What is a Ramachandran plot?
• What is the simplest way to calculate a numerical derivative?
• How do you calculate the next position in molecular dynamics?
• What defines a saddle point, a minimum or a maximum on an energy surface?

Minimization and Optimization with a Force Field

• In an iterative optimization, why is step size critical?
• First derivative methods solve for a direction toward the minimum.
• Second derivative methods solve for the direction AND size of the step.

Parameters for Molecular Mechanics

• Compare parameter optimization to structure minimization
• Using the formaldehyde example from Slide 5, how many additional, unique data for fitting would be available from the Hessian matrix?
• Ignoring the van der Waals parameters (again referring to slide 5), the structure and the Hessian give ____ values from which to determine 9 parameters. Does this seem like enough to you? Defend your answer.

  NOTE: In thinking this problem through, be sure you think about the symmetry of the Hessian matrix AND the symmetry of the structure.

  NOTE: THIS IS A TRICKY QUESTION. You may need to block out the Hessian matrix to count up the number of unique terms.