C687 Midterm Questions and Answers

A subset of the following questions will appear on the mid-term exam. No questions will appear on the exam that are not included in this list. The mid-term exam is scheduled for 1:30-3pm, Wednesday, April 7, in room A400.

Questions are in bold. Acceptable answers are in plain text. Note that more than one acceptable answer may exist for some questions.

Visualization

• Q: What is "visualization"?
  A: changing the view to improve the information content.

• Q: Identify all types of Visualization Models in the list below:
  1. Graphical Interpretation
  2. Simplification
  3. Symbolic Reduction
  4. Analgization
  5. Mathethmatical Description
  6. All of the above
  7. none of the above
  A: 2, 4, and 5

• Q: Identify all types of Visualization Models in the list below:
  1. Fundamental Cartoon
  2. Comprehensive Perspective
  3. Didactical Illustration
  4. Dynamic Animation
  5. All of the above
  6. none of the above
  A: 3

• Q: Identify all types of Visualization Models in the list below:
  1. Mathethmatical Description
  2. Mathethmatical Generalization
  3. Mathethmatical Correlation
  4. Mathethmatical Simplification
  5. All of the above
  6. none of the above
  A: 1

• Q: True or False: The molecular modeling specialist must judge whether proper techniques have been used ("is the result accurate?").
  A: True

• Q: True or False: The molecular modeling specialist must judge whether proper controls and control experiments have been used ("is the result reliable or sgnificant?").
  A: True

• Q: True or False: The molecular modeling result depends as much on the quality of the modeler as the quality of the modeling technique.
  A: True

• Q: True or False: The molecular modeling specialist must judge whether sufficient parameter space been searched if not all possibilities have been calculated.
  A: True

• Q: True or False: The molecular modeling specialist must judge whether the basis set has been sufficiently large to cover all appropriate possibilities.
  A: True

• Q: A stand-alone computer must have:
  1. CPU
  2. memory
  3. disk
  4. graphics processor
  5. monitor
  6. keyboard
  7. All of the above
  8. none of the above
  A: 7

• Q: True or False: A "local computer" is the computer with which you physically interact during your computing session.
  A: True

• Q: True or False: A "remote computer" is the computer with which you interact through a network (e.g., via 'telnet') from a local computer.
  A: True

• Q: Why use UNIX workstations?
  1. UNIX workstations are easier to program and support.
  2. UNIX workstations have historically been used for scientific computing.
  3. The specific parts of a UNIX workstation are still faster than parts of a PC or Mac workstation.
  4. The interaction of parts of a UNIX workstation is still faster with UNIX workstations than with PCs and Macs.
  5. All of the above
  6. none of the above
  A: 1, 2, and 4

• Q: In practice, a "networked computer" may consist of:
  1. monitor and keyboard of a local workstation
  2. monitor and keyboard of a remote workstation
  3. CPU, memory, graphics processor of a local workstation
  4. CPU, memory, graphics processor of a remote workstation
  5. disk in local workstation
  6. disk in remote workstation
  7. All of the above
  8. none of the above
  A: 1, 3, 4, 5, and 6

Database Searching, Sequence Alignment, Homology Modeling,
and Evaluation of the Quality of a Molecular Model

• Q: True or False: Sequence alignments are evolutionary hypotheses.
  A: True

• Q: True or False: "sequence homology" is a binary property. Two sequences ARE homologous or ARE NOT homologous.
  A: True.

• Q: True or False: "sequence homology" is a quantitative measure. The percentage of homology between two sequences is an appropriate description.
  A: False.

• Q: True or False: "sequence identity" is a quantitative measure. The percentage of sequence identity between two sequences is an appropriate description.
  A: True.

• Q: True or False: "sequence identity" is a binary property. Two sequences ARE identical or ARE NOT identical.
  A: False

• Q: If two sequences are greater than 100 residues, and they have >25% sequence identity, are they related?
  A: Probably YES.

• Q: If two sequences are greater than 100 residues, and they have >15% and <25% sequence identity, are they related?
  A: Teh amount of sequence identity is too ambiguous to answer this question.

• Q: If two sequences are greater than 100 residues, and they have <15% sequence identity, are they related?
  A: Probably NO.

• Q: If two sequences are less than 100 residues, and they have >25% sequence identity, are they related?
  A: Due to the relatively short sequence lengths, this question can't be answered with confidence.

• Q: If two sequences are less than 100 residues, and they have >15% and <25% sequence identity, are they related?
  A: Due to the relatively short sequence lengths, this question can't be answered with confidence.

• Q: If two sequences are less than 100 residues, and they have <15% sequence identity, are they related?
  A: Due to the relatively short sequence lengths, this question can't be answered with confidence.

• Q: Identify all sequence alignment scoring matrices in the following list (select all that apply):
  1. codon substitution scoring matrices
  2. electrostatic scoring matrices
  3. hydrophobicity scoring matrices
  4. loops & gaps scoring matrices
  5. hydrogen bond scoring matrices
  6. all of the above
  7. none of the above
  A: 1 and 3

• Q: Identify all sequence alignment scoring matrices in the following list (select all that apply):
  1. biosynthetic frequency matrices
  2. sequence homology matrix
  3. mutation frequency scoring matrices
  4. sequence identity matrix
  5. residue volume matrices
  6. all of the above
  7. none of the above
  A: 3 and 4

• Q: Which sequence alignment scoring matrices include secondary structure information?
  A: None! This is a trick question.

• Q: What is a gap in a sequence alignment?
  A: A segment in a sequence that does not have residues that correspond to existing residues in the other aligned sequence or sequences.

• Q: What is a loop in a sequence alignment?
  A: A segment in a sequence for which there are no corresponding residues in the other aligned sequence or sequences.

• Q: True or False: sequence alignment methods often have difficulty with regularly repeating segments (e.g. repeating sequences in helices) or pseudo-symmetric dimers.
  A: True.

• Q: True or False: gaps and loops usually exist within structurally conserved regions.
  A: False.

• Q: Sequence alignments can be used to perform the following (select all that apply):
  1. secondary structure prediction
  2. designing PCR primers
  3. development of molecular interaction scales
  4. inferring functional importance from sequence conservation
  5. testing evolutionary hypotheses (i.e., phylogenetic analyses)
  6. all of the above
  7. none of the above
  A: 2, 4, 5

• Q: True or False: Specific types of side chain rotamer angles are found within specific types of structural motifs.
  A: True.

• Q: True or False: about 80% of identical residues have the same rotameric state for all side chains.
  A: True

• Q: True or False: about 70% to 75% of mutated residues have the same rotameric state for all side chains.
  A: True

• Q: Identify options available for evaluating the quality of a protein model (select all that apply):
  1. evaluation of solvent-accessible hydrogen bond donors
  2. evaluation of mainchain torsion angle distributions
  3. evaluation of peptide bond angle distributions
  4. evaluation of solvent-accessible polar groups
  5. evaluation of chirality of alpha-carbon atoms
  6. all of the above
  7. none of the above
  A: 2, 3, 5

• Q: Identify options available for evaluating the quality of a protein model (select all that apply):
  1. evaluation of bond length distributions
  2. evaluation of the model's free energy thermodynamic cycle ("delta-delta-G")
  3. evaluation of bond angle distributions
  4. evaluation of planarity of aromatic ring systems
  5. evaluation of electrostatic charge distributions
  6. all of the above
  7. none of the above
  A: 1, 3, 4

• Q: Identify options available for evaluating the quality of a protein model (select all that apply):
  1. evaluation of planarity of sp2-hybridized end groups
  2. evaluation of van der Waals overlaps ("bump check")
  3. evaluation of hydrogen bond qualities
  4. evaluation of the distribution of polar amino acids on surface & interior
  5. evaluation of backbone atom types
  6. all of the above
  7. none of the above
  A: 1, 2, and 4

• Q: Identify options available for evaluating the quality of a protein model (select all that apply):
  1. evaluation of energies of force field cross terms
  2. evaluation of the distribution of non-polar amino acids on surface & interior
  3. evaluation of buried hydrogen bond donors
  4. evaluation of solvent-accessible hydrogen bond acceptors
  5. evaluation of 3D RMSD superpositions of model structures and template structures
  6. all of the above
  7. none of the above
  A: 2, 3, and 5

• Q: Identify options available for evaluating the quality of a protein model (select all that apply):
  1. evaluation of the geometry of secondary structural elements
  2. evaluation of non-bond energies
  3. evaluation of buried polar groups
  4. evaluation of the location of secondary structural elements
  5. evaluation of the model's radius of gyration
  6. all of the above
  7. none of the above
  A: 1, 3, and 4

• Q: Identify options available for evaluating the quality of a protein model (select all that apply):
  1. evaluation of the model's surface area
  2. evaluation of buried hydrogen bond acceptors
  3. evaluation of the model's center of mass
  4. evaluation of chirality of serine side chains
  5. evaluation of chirality of threonine side chains
  6. all of the above
  7. none of the above
  A: 1, 2, and 5

• Q: What is a Ramachandran plot?
  A: a graph of a protein's mainchain torsion angle distribution (i.e., phi angle vs psi angle for each residue).

• Q: True or False: Incorrectly folded protein models almost always have larger surface areas than correctly folded protein models.
  A: True.

• Q: How many unsatisfied hydrogen bond donors or hydrogen bond acceptors are acceptable in an ideal high-quality protein model?
  A: Ideally, there should be ZERO unsatisfied hydrogen bond donors or hydrogen bond acceptors.

• Q: True or False: The total energy of two or more homology models can be used to determine which homology model is correct.
  A: False.

• Q: Identify databanks and databases that contain 3D structures (select all that apply):
  1. the Swis-Prot database
  2. the Protein Data Bank
  3. the TIGR Database
  4. the EC Enzyme Database
  5. the Cambridge Structure Database
  6. all of the above
  7. none of the above
  A: 2 and 5

• Q: Identify databanks and databases that contain 3D structures (select all that apply):
  1. the NDB (Nucleic Acid Databank)
  2. the PIR (Protein Information Resource)
  3. the GenBank Database (National Center for Biotechnology Information)
  4. the PROSITE database
  5. all of the above
  6. none of the above
  A: 1

• Q: What is the difference between a DATABANK and a DATABASE?
  A: A DATABASE stores information in a parallel, relational, or "interconnected" arrangement, allowing for rapid search and retrieval by a multidimensional search engine using a query language. A DATABANK stores information in a serial, or "linear" arrangement, requiring an exhaustive search and retrieval by a one-dimensional search engine, usually using a "string search".

• Q: Identify information that you can use to search for information (select all that apply):
  1. search by taxonomy
  2. search by taxon
  3. search by literature reference
  4. search by keyword
  5. search by sequence similarity of local alignments
  6. search by 3D coordinates
  7. search by function
  8. all of the above
  9. none of the above
  A: 8

Energy Minimization and Molecular Dynamics

• Q: What are force field "cross terms"?
  A: Cross terms are combinations of the four general bond terms.

• Q: When must you include cross terms?
  A: Cross terms are required for high-precision minimizations, such as minimizations required for vibrational analyses.

• Q: Name the "covalent bond terms" in most classical newtonian force fields.
  A: bond term, angle term, dihedral angle term, and planar term.

• Q: Name the "nonbond terms" in most classical newtonian force fields.
  A: van der Waals term and electrostatic term.

• Q: When would you choose to use a Morse bond term?
  A: A Morse bond term is required for high-precision minimizations, such as minimizations required for vibrational analyses, or for dynamics that are far from a minimum.

• Q: Name the "universal force field" appropriate for all molecules.
  A: There is no universal force field! This is a trick question.

• Q: A force field parameter (e.g., "spring constant" for stretching a bond) is a:
  1. Microscopic Descriptor (e.g., a description of the exact energy needed to stretch the bond)
  2. Practical Descriptor (e.g., a description of bond stretch energy that interacts with other terms to produce realistic models).
  A: a Practical Descriptor

• Q: Name the steps necessary to "plug" a new parameter into a force field.
  A: Force field parameters should NEVER just be plugged into a force field without careful testing. This is a trick question!

• Q: A diagonal force field has:
  A: no cross terms

• Q: A matrix force field has:
  A: cross terms

• Q: A Class II force field has:
  A: parameters derived from quantum mechanics

• Q: A "Fast" force field has:
  A: only dihedral torsion angle terms and non-bond terms

• Q: What terms do some (less accurate) force fields hold fixed in order to speed up dynamics calculations?
  A: bond, angle, and planar (improper torsion) terms.

• Q: Which force field or force fields available in InsightII are parameterized only for standard amino acids?
  A: The CFF91 force field.

• Q: Which force field or force fields available in InsightII are parameterized only for standard amino acids and nucleotides?
  A: The AMBER and AMBER95 force fields.

• Q: Which force field or force fields available in InsightII are parameterized for many types of atoms?
  A: The CVFF and ESFF force fields.

• Q: What force field terms are often scaled for vicinal atom pairs?
  A: Non-bond force field terms.

• Q: What are "Periodic Boundary Conditions"?
  A: A solute surrounded by an isolated cube of solvent is replicated periodically in three dimensions to represent an infinitely large bulk or crystalline environment.

• Q: How can you simulate a system with infinite size?
  A: By using periodic boundary conditions.

• Q: What is a "Minimim Image Model"?
  A: A Minimum Image Model within Periodic Boundary Conditions allows each real molecular model in the central unit cell to interact with only one image of each real molecular model in the central cell or nearest adjacent cells.

• Q: What is an "Explicit Image Model"?
  A: An Explicit Image Model within Periodic Boundary Conditions allows each real molecular model in the central unit cell to interact with all images of all molecular models in the central unit cell or the nearest adjacent cells.

• Q: What dielectric constant is generally used to simulate the dielectric medium inside a protein structure?
  A: 4

• Q: What is the dielectric constant of a vacuum?
  A: 1

• Q: What is the dielectric constant at the surface of a protein?
  A: about 10

• Q: If solvent molecules are explicitly included in the system, what dielectric constant should be used?
  A: 1

• Q: The dielectric constant is approximately uniform for:
  1. only small molecules
  2. only large molecules
  3. both small and large molecules
  
  A: small molecules

• Q: What force field terms are most responsible for the majority of calculation times for large molecules?
  A: the non-bond force field terms (i.e., van der Waals and electrostatic interaction terms).

• Q: What is a non-bond energy cutoff value?
  A: Non-bond energies are only calculated for atom pairs that are separated by distances smaller than the non-bond energy curoff value.

• Q: What nonbond cutoff value should be used for proteins?
  A: at least 15 angstroms

• Q: What nonbond cutoff value should be used for nucleic acids?
  A: at least 20 angstroms

• Q: What nonbond cutoff value should be used for aliphatic polymers?
  A: at least 10 angstroms

• Q: What nonbond cutoff value should be used for carbohydrates?
  A: at least 20 angstroms

• Q: What is the Cell Multipole Method?
  A: The electrostatic potential felt by atom i may be divided into a near-field potential from surrounding atoms, and a far-field potential due to the rest of the atoms. The Cell Multipole method represents the far-field potentials as the general potential originating at the center of cells far from atom i.

• Q: What is the Ewald Summation Method?
  A: A Fourier Transform method to evaluate the electrostatic potentials of periodic systems.

• Q: Identify one or more types of constraints that can be applied to make calculations faster:
  1. Torsion constraints
  2. Fixed Atom constraints
  3. Tethered Atom constraints
  4. Distance Constraints
  5. Template Force constraints
  6. All of the above
  7. none of the above
  A: 2

• Q: When minimizing the energy of a molecular model, what derivative value should you select to ensure that your molecule has reached a minimum energy?
  A: There is no exact answer---this is a trick question! Only a "molecular modeling experiment" can determine if you have reached a sufficient energy minimum during minimization calculations for your purposes.

• Q: When should you use the Steepest Decents algorithm?
  1. When you are far from the minimum.
  2. When you are near "saddle points" on the energy surface.
  3. When you have nonstandard amino acid or nucleic acid residues
  4. When you minimize with cross terms
  5. All of the Above.
  6. None of the Above.
  A: 1 and 2

• Q: Identify limitations that may prevent you from using a matrix-based minimization method, such as the Newton-Raphson or VAO9A algorithms. Select one or more correct answers.
  
  1. Minimizing a model with a Morse Term
  2. Minimizing a model that is far from the energy minimum.
  3. Minimizing a model with the Amber95 force field parameters
  4. Minimizing a model with more than 200 atoms
  5. Minimizing a model with fixed atoms
  6. All of the above
  7. None of the Above
  A: 2 & 4

• Q: What is the basic difference between molecular dynamics and simulated annealing?
  A: Simulated annealing calculations run extra dynamics steps at a cooler temperatures before the final minimization.

• Q: What is the time step for most molecular dynamics calculations?
  A: 1 to 3 femtoseconds

• Q: What is a cluster graph?
  A: A graph showing the RMSD difference between each pair of conformations of an ensemble of conformers.

• Q: Identify limitations that may prevent you from using the Conjugate Gradients minimization method. Select one or more correct answers.
  
  1. Minimizing a model that is far from the energy minimum
  2. Minimizing a model with a Morse Term
  3. Minimizing a model with a potential energy surface with many saddle points
  4. Minimizing a model with the Amber95 force field parameters
  5. Minimizing a model with more than 200 atoms
  6. All of the above
  7. None of the Above
  A: 1 & 3

• Q: how do you determine if a Discover or Discover_3 minimization calculation has reached the derivative threshold that you requested?
  A: you must examine the contents of the file that ends with ".inp".

• Q: The units of the Discover or Discover_3 miniization derivative is:
  1. kcal mol^-1
  2. kcal mol^-1 angstrom^-1
  3. kcal angstrom^-1
  4. None of the Above
  A: 2

• Q: Discover and Discover_3 miniizations are reported as "successful" if:
  1. The minimum derivative is less than the derivative threshold
  2. The maximum derivative is less than the derivative threshold
  3. The average derivative is less than the derivative threshold
  4. The total number of iterations is reached.
  5. All of the above
  6. None of the Above
  A: 2

• Q: To retain the "core conformation" of a structure during minimization:
  (select all that apply)
  1. minimize the structure with fixed heavy atoms
  2. minimize the structure with fixed backbone
  3. minimize the structure with fixed structually conserved regions
  4. all of the above
  5. none of the above
  A: 4

• Q: Quantum Mechanical Calculations are required for:
  (select all that apply)
  1. photon absorption
  2. bond formation
  3. protein folding
  4. acid/base reactions
  5. all of the above
  6. none of the above
  A: 1, 2, and 4

• Q: What is the "Active Analog Approach"?
  A: conformers of active analogs are systematically generated via torsion angle rotations; only conformers that match the geometry of an active analog that has few degrees of freedom (i.e., is relatively rigid or conformationally restricted) are selected for further analysis.

• Q: What is the Rigid Rotor Technique?
  A: conformers are systematically generated via torsion angle rotations; no energy minimization is performed after each torsion angle rotation.

• Q: What is the Dihedral Driver Technique?
  A: conformers are systematically generated via torsion angle rotations; energy minimization IS performed after each torsion angle rotation.

• Q: What is the difference between the Rigid Rotor Technique and the Dihedral Driver Technique?
  A: energy minimization is performed after each torsion angle rotation in the Dihedral Driver Technique; no energy minimization is performed in the Rigid Rotor Technique.

• Q: How do you prove that a Monte Carlo search has sampled sufficiently long enough?
  A: Start from different starting points; if each run generates the same result, the calculation has converged to the same ensemble.

• Q: What conformational search method is best for ring systems?
  A: The Monte Carlo method.

• Q: Name the conformational search method that uses the following protocol:
  
  1. move atomic coordinates in a random direction
  2. minimize the structure
  3. • if the conformation's absolute energy is below a pre-set threshold, save the new conformation
     • if the conformation's absolute energy is above a pre-set threshold, and a random number is selected that is greater than a "temperature factor", save the new conformation
     • if the conformation's absolute energy is above a pre-set threshold, and a random number is selected that is greater than a "temperature factor", return to the original conformation
  4. return to the first step and repeat many times.
  5. reduce the "temperature factor" and repeat steps 1-4. Continue to reduce the energy threshold until the energy is near a minimum.
  A: the Monte Carlo method.

• Q: Name the conformational search method that uses the following protocol:
  
  1. move atomic coordinates in a random direction
  2. • if the conformation's absolute energy is below a pre-set threshold, increase the average atomic displacements during randomization
     • if the conformation's absolute energy is above a pre-set threshold, reduce the average atomic displacements during randomization
  3. return to the first step and repeat many times.
  A: the Molecular Dynamics method.

• Q: Name the conformational search method that uses the following protocol:
  
  1. move atomic coordinates in a random direction
  2. • if the conformation's absolute energy is below a pre-set threshold, increase the average atomic displacements during randomization
     • if the conformation's absolute energy is above a pre-set threshold, reduce the average atomic displacements during randomization
  3. return to the first step and repeat many times.
  4. reduce the pre-set energy threshold and repeat steps 1-3. Continue to reduce the energy threshold until the energy is near a minimum.
  A: the Simulated Annealing method.

• Q: What is the RATTLE method?
  A: bond lengths, or bond lengths and bond angles, are held relatively fixed.

• Q: What is the advantage of the RATTLE method?
  A: the molecular dynamics time step can be increased from 1 fsec to 3 fsec.

• Q: What is the practical advantage of holding angles fixed via the RATTLE method?
  A: Almost none! (Only holding bonds fixed substantially improves computation speed.)

• Q: What is the minimum time required to equilibrate most systems during molecular dynamics?
  A: at least 10 picoseconds.

• Q: Which technique is least able to ensure complete sampling of conformational space?
  
  1. Systematic Search Methods
  2. Monte Carlo Methods
  3. Molecular Dynamics Methods
  4. All methods are equal
  5. The answer depends on the system being studied
  6. None of the Above
  A: 3

• Q: True or False: energies of systems with different numbers of bonds can be directly compared.
  A: False

• Q: True or False: energies of systems with different numbers of atoms can be directly compared.
  A: False

• Q: True or False: energies of systems with the same total charge can always be directly compared.
  A: False

• Q: True or False: energies of systems with the same bonds and atoms can be directly compared.
  A: True

• Q: What are the requirements for a successful Free Energy Peturbation method?
  Assume that
  

  A + Protein    <--->    A:Protein
  
    ^                      ^
    |                      |
  
  B + Protein    <--->    B:Protein
  

  (select all that apply)
  1. Changes between A and B must be small
  2. A and B must bind to the protein in the same general location and orientation
  3. solvent must be excluded
  4. The free energy change must be large to overcome inaccuracies in this method
  5. Only energy-minimized cnformers can be used in this method.
  6. All of the above
  7. none of the above
  A: 1, 2, and 5

• Q: True or False: (dG1 - dG2) = (dG3 - dG4)
  Assume that
  

                 dG1
  A + Protein    --->    A:Protein
  
    ^                     ^
    | dG4                 | dG3
  
                 dG2
  B + Protein    --->    B:Protein
  
  dG1 = A:Protein - (A + Protein)
  dG2 = B:Protein - (B + Protein)
  dG3 = A:Protein - B:Protein
  dG4 = (A + Protein) - (B + Protein)
  

  A: True

• Q: True or False: (dG1 - dG2) = (dG3 - dG4)
  Assume that
  

                 dG1
  A + Protein    --->    A:Protein
  
    ^                     ^
    | dG3                 | dG4
  
                 dG2
  B + Protein    --->    B:Protein
  
  dG1 = A:Protein - (A + Protein)
  dG2 = B:Protein - (B + Protein)
  dG3 = (A + Protein) - (B + Protein)
  dG4 = A:Protein - B:Protein
  

  A: False

• Q: True or False: (dG1 - dG2) = (dG3 - dG4)
  Assume that
  

                 dG2
  A + Protein    --->    A:Protein
  
    ^                     ^
    | dG4                 | dG3
  
                 dG1
  B + Protein    --->    B:Protein
  
  dG1 = B:Protein - (B + Protein)
  dG2 = A:Protein - (A + Protein)
  dG3 = A:Protein - B:Protein
  dG4 = (A + Protein) - (B + Protein)
  

  A: False

• Q: True or False: (dG1 - dG2) = (dG3 - dG4)
  Assume that
  

                 dG2
  A + Protein    --->    A:Protein
  
    ^                     ^
    | dG3                 | dG4
  
                 dG1
  B + Protein    --->    B:Protein
  
  dG1 = B:Protein - (B + Protein)
  dG2 = A:Protein - (A + Protein)
  dG3 = (A + Protein) - (B + Protein)
  dG4 = A:Protein - B:Protein
  

  A: True

Docking & Electrostatics

• Q: True or False: Electrostatics can be used to measure relative binding constants and relative association rates.
  A: True.

• Q: True or False: Electrostatics can be used to measure absolute binding constants and relative association rates.
  A: False.

• Q: True or False: Electrostatics can be used to measure relative binding constants and absolute association rates.
  A: False.

• Q: True or False: Electrostatics can be used to measure absolute binding constants and absolute association rates.
  A: False.

• Q: What is "polarity"?
  A: The density of charged groups and dipolar groups

• Q: What is "polarization"?
  A: The potential for reorganizing charges, orienting dipoles, and inducing dipoles

• Q: A folding protein has (select all that apply):
  1. high polarity, high polarizability
  2. high polarity, low polarizability
  3. low polarity, high polarizability
  4. low polarity, low polarizability
  A: 1

• Q: A folded protein has (select all that apply):
  1. high polarity, high polarizability
  2. high polarity, low polarizability
  3. low polarity, high polarizability
  4. low polarity, low polarizability
  A: 2

• Q: What is "the measure of non-polar surface area of a conformer"?
  A: lipophilicity

• Q: What is "the measure of the partition coefficient of a molecule between water and an organic solvent"?
  A: hydrophobicity

• Q: What is "lipophilicity"?
  A: "the measure of non-polar surface area of a conformer"

• Q: What is "hydrophobicity"?
  A: "the measure of the partition coefficient of a molecule between water and an organic solvent"

• Q: What solvent is often cited as having the same dielectric constant and (hydrogen bond/molecular weight) ratio that is similar to the "core" of a protein?
  A: octanol

• Q: True or False: lipophilicity is used as a qualitative measure of free energy of solvation.
  A: False

• Q: True or False: lipophilicity is used as a quantitative measure of free energy of solvation.
  A: False

• Q: True or False: hydrophobicity is used as a qualitative measure of free energy of solvation.
  A: True

• Q: True or False: hydrophobicity is used as a quantitative measure of free energy of solvation.
  A: False

• Q: Electrostatics can be used to measure:
  1. changes in acid/base reactions
  2. changes in pKa values
  3. changes in electron transport
  4. changes in redox midpoints
  5. changes in stabilization energies
  6. All of the above
  7. none of the above
  A: 2, 4, and 5

• Q: True or False: the polarization of large protein dipole reorientations can be represented by a dielectric model.
  A: False

• Q: True or False: the polarization of large protein dipole reorientations can be represented by explicit charge distributions.
  A: True

• Q: True or False: the polarization of small protein dipole reorientations can be represented by a dielectric model.
  A: True

• Q: True or False: the polarization of small protein dipole reorientations can be represented by explicit charge distributions.
  A: True

• Q: Dipole reorientations within a protein approximate a dielectric medium with a dielectric constant of:
  A: 2.5 to 4

• Q: Charge rearrangements within a protein approximate a dielectric medium with a dielectric constant of:
  A: greater than 30

• Q: electronic polarizabilities within a protein approximate a dielectric medium with a dielectric constant of:
  A: 2 to 2.5

• Q: What effects within a protein cause the protein to approximate a dielectric medium with a dielectric constant greater than 30?
  1. Dipole reorientations
  2. Charge rearrangements
  3. Electronic polarizabilities
  4. All of the above
  5. none of the above
  A: 2

• Q: What effects within a protein cause the protein to approximate a dielectric medium with a dielectric constant of 2 to 2.5?
  1. Dipole reorientations
  2. Charge rearrangements
  3. Electronic polarizabilities
  4. All of the above
  5. none of the above
  A: 3

• Q: What effects within a protein cause the protein to approximate a dielectric medium with a dielectric constant of 2.5 to 4?
  1. Dipole reorientations
  2. Charge rearrangements
  3. Electronic polarizabilities
  4. All of the above
  5. none of the above
  A: 1

• Q: What is the name of the electrostatic field created by an atom as it responds to electrostatic fields from other atoms?
  A: The "reaction field".

• Q: What is "QSAR"?
  A: Quantitative Structure-Activity Relationships

• Q: True or False: 2D QSAR methods usually focus only on the initial interaction between a ligand and receptor; all subsequent processes leading to biological function are generally not taken into account.
  A: True

• Q: 2D QSAR techniques include:
  1. chemical information systems
  2. reaction databases
  3. pharmacophore generation based on covalent structure
  4. all of the above
  5. none of the above
  A: 4

• Q: 3D QSAR techniques include:
  1. de novo ligand design
  2. analyses of principle geometric components
  3. pharmacophore generation based on conformation
  4. prediction of properties based on types of functional groups
  5. all of the above
  6. none of the above
  A: 1, 2, and 3

• Q: True or False: The binding conformation must exist among the low-energy conformers generated during an exhaustive conformational search of all conformational space.
  A: False.

• Q: True or False: The binding conformation is likely to exist among the low-energy conformers generated during an exhaustive conformational search of all conformational space.
  A: True.

• Q: What are "bioisosteric ligands"?
  A: ligands that have all necessary functional groups that interact with the binding site in the same way.

• Q: What is a "pharmacophore"?
  A: a ligand with all necessary functional groups in the correct conformation for binding.
  (The literal Greek translation is "medicine carrier")

• Q: What is the definition of "CoMFA"?
  A: "Comparitive Molecular Field Analysis"

• Q: Describe CoMFA (Comparitive Molecular Field Analysis).
  A: conformers are superimposed based on Molecular Interaction Fields to find common biologically-active properties.

• Q: conformers can be superimposed based on (select all that apply):
  1. atom-by-atom pairwise RMSD fit
  2. fit of Molecular Interaction Fields and associated properties
  3. fit of molecular surfaces
  4. all of the above
  5. none of the above
  A: 4

• Q: What are the most important problems with CoMFA?
  1. depends on initial conformation of rigid ligands
  2. depends on molecular alignments
  3. depends on parameters describing Molecular Interaction Fields
  4. depends on scoring schemes
  5. doesn't explicitly account for hydrogen bonds
  6. All of the above
  7. None of the Above
  A: 1 and 4

• Q: What are the most important problems with docking methods?
  1. requires information about the binding site before the docking can proceed
  2. approximate methods are too inaccurate to generate meaningful results
  3. scoring schemes are not reliable
  4. must consider water molecules in the active site
  5. docked receptors are rigid
  6. All of the above
  7. None of the Above
  A: 3 and 5

• Q: Name the automated ligand design method that covers all possibilities
  A: There is NO ligand design method that covers all possibilities---this is a trick question!

• Q: Which automated ligand design method is better for ligands with conformational and structural variations?
  
  1. the atom-by-atom ligand design method
  2. the fragment-addition ligand design method
  3. the pharmacore-pattern ligand design method
  4. all methods are equal
  A: the atom-by-atom ligand design method

• Q: Which automated ligand design method is more likely to generate ligands that are chemically or synthetically plausible?
  
  1. the atom-by-atom ligand design method
  2. the fragment-addition ligand design method
  3. the pharmacore-pattern ligand design method
  4. all methods are equal
  A: the fragment-addition ligand design method

• Q: Which automated ligand design method is faster?
  
  1. the atom-by-atom ligand design method
  2. the fragment-addition ligand design method
  3. the pharmacore-pattern ligand design method
  4. all methods are equal
  A: the fragment-addition ligand design method

• Q: Which automated ligand design method is best for ring structures?
  
  1. the atom-by-atom ligand design method
  2. the fragment-addition ligand design method
  3. the pharmacore-pattern ligand design method
  4. all methods are equal
  A: the pharmacore-pattern ligand design method

• Q: Which automated ligand design method is best if you have no receptor structure available?
  
  1. the atom-by-atom ligand design method
  2. the fragment-addition ligand design method
  3. the pharmacore-pattern ligand design method
  4. all methods are equal
  A: the pharmacore-pattern ligand design method

• Q: Match the "Interaction" with the "Free Energy" according to Bohm's Ligand Design Scoring Function
  

  Interaction	Free Energy
  1: loss of translational & rotational motion of ligand	A: -4.7 kJ/mol
  2: loss of freedom for each rotatable bond of ligand	B: -8.3 kJ/mol
  3: generation of ideal hydrogen bond	C: +5.4 kJ/mol
  4: generation of ideal ionic interaction	D: -0.17 kJ/ang2
  5: lipophilic contact	E: +1.4 kJ/mol

  Answer: 1=C, 2=E, 3=A, 4=B, 5=D

• Q: According to the LUDI Ligand Design Empirical Scoring Function, what is the distance range (from hydrogen to hydrogen bond acceptor) for an ideal hydrogen bond?
  A: 1.7 to 1.9 angstroms

• Q: According to the LUDI Ligand Design Empirical Scoring Function, what is the distance range (from hydrogen to hydrogen bond acceptor) for any hydrogen bond?
  A: 1.3 to 2.5 angstroms

• Q: According to the LUDI Ligand Design Empirical Scoring Function, what is the angle range (from hydrogen bond donor, to hydrogen, to hydrogen bond acceptor) for an ideal hydrogen bond?
  A: -150 to +150 degrees

• Q: According to the LUDI Ligand Design Empirical Scoring Function, what is the angle range (from hydrogen bond donor, to hydrogen, to hydrogen bond acceptor) for any hydrogen bond?
  A: -100 to +100 degrees

• Q: According to the LUDI Ligand Design Empirical Scoring Function, how many square angstroms of lipophilic contact equal 1 ideal hydrogen bond (in terms of interaction energies)?
  A: 60 angstroms² equals 1 ideal hydrogen bond.

• Q: What types of interaction energies are incorporated into automated ligand design methods? Select all that apply.
  1. electrostatic interactions
  2. hydrogen bond interactions
  3. ionic interactions
  4. hydrophobic interactions
  5. all of the above
  6. none of the above
  A: 5

• Q: What is the "Link Score" of a fragment-based ligand design method?
  A: A score that measures how well the new fragment can attach to the existing fragment by a covalent bond, assuming that the new fragment is oriented for optimized binding, and the existing fragment doesn't change it's initial orientation.

UNIX Commands

1. Q: How can you find all files in your home directory & all sub-directories that end with .psv?
   A: find $HOME -name "*psv" -print

2. Q: How can you list all lines of zinc_finger.out that include the text "Writing"?
   A: more zinc_finger.out | grep Writing

3. Q: How can you list ALL files in a directory?
   A: ls -a

4. Q: How can you rename a file named junk.data to the name published.data?
   A: mv junk.data published.data

5. Q: How can you learn more about the ls command in a UNIX shell?
   A: man ls

6. Q: How can you learn more about commands related to the keyword priority?
   A: man -k priority

7. Q: How can you delete all files that end with .ps in your current working directory?
   A: rm *.ps

8. Q: How can you determine your present working directory?
   A: pwd

9. Q: How can you list your currently running processes?
   A: ps -ef | grep $LOGNAME

10. Q: How can you change directories to your home directory?
    A: cd or cd $HOME or cd path_to_your_home_directory

11. Q: How can you list the date & time that file master.data was last modified?
    A: ls -l master.data

12. Q: How can you set the permissions for your file named master.data so that only you can read, write, and execute it?
    A: chmod 700 master.data

13. Q: How can you list the most active processes on your workstation?
    A: top

14. Q: How can you list all users currently logged on to your workstation?
    A: who

15. Q: How can you list the contents of file master.data screen page-by-screen page?
    A: more master.data

16. Q: How can you list the first lines of the file master.data?
    A: head master.data or head -10 master.data

17. Q: How can you list the first 5 lines of the file master.data?
    A: head -5 master.data

18. Q: How can you list the last lines of the file master.data?
    A: tail master.data or tail -10 master.data

19. Q: How can you list the last 5 lines of the file master.data?
    A: tail -5 master.data

20. Q: How can you list the differences between original.data and new.data?
    A: diff original.data new.data

21. Q: How can you list the size of your home directory, including all sub-directories?
    A: du -sk $HOME

22. Q: How can you list the size of all files in your present working directory?
    A: du -sk *

23. Q: How can you list the size of all files in your directory, sorted by size (smallest listed first)?
    A: du -sk * | sort -n

24. Q: How can you list the size of all files in your directory, sorted by size (largest listed first)?
    A: du -sk * | sort -rn

25. Q: How can you list the size of the 10 largest files in your directory, sorted by size (largest listed first)?
    A: du -sk * | sort -rn | head -10

26. Q: How can you create a new directory named calc.results?
    A: mkdir calc.results

27. Q: How can you remove a directory named calc.results and it's contents?
    A: rm -r calc.results

28. Q: How can you transfer files between worktations that don't share disks across the network?
    A: use ftp

29. Q: How do you list the contents of the directory calc.results without changing directories?
    A: ls calc.results

30. Q: How do you list the existence of a directory calc.results in your current working directory?
    A: ls -d calc.results

31. Q: How do you list the process number of your process named fdiscover?
    A: ps -ef | grep $LOGNAME | grep fdiscover

32. Q: How do you immediately kill process 3278 (assumng that you own this process)?
    A: kill -9 3278

33. Q: How do you suspend process 3278 (assumng that you own this process)?
    A: kill -23 3278

34. Q: How do you restart process 3278 (assumng that you own this process)?
    A: kill -25 3278

35. Q: How do you list the files of the parent directory of your current working directory?
    A: ls ../

36. Q: How can you list the previous commands that you typed?
    A: history

37. Q: How can you repeat your last command?
    A: !!

38. Q: How can you repeat the 153rd command that you've typed?
    A: !153

39. Q: How can you repeat the last command that started with mo that you typed?
    A: !mo

40. Q: How can you execute a command named run.calc in the background?
    A: run.calc &

41. Q: How can you print an expanded list of all processes?
    A: ps -ef

42. Q: How can you interrupt the current process running in the foreground?
    A: <control-c>

43. Q: How can you suspend the current process running in the foreground?
    A: <control-z>

44. Q: How can you display background and suspended processes?
    A: jobs

45. Q: How can you remove suspended process #1?
    A: kill %1

46. Q: How can ou display the current, most computer-intensive commands?
    A: top

47. Q: How can you display the operating system statitistics?
    A: osview

48. Q: How can you graphically display the operating system statitistics?
    A: gr_osview

49. Q: How can you end your terminal session or close your UNIX shell?
    A: logout or exit

50. Q: How can you change your password?
    A: passwd

51. Q: How can you print the current date & time?
    A: date

52. Q: How can you log onto a remote workstation named stereo3?
    A: telnet stereo3

53. Q: How can you print a list of disks and current disk capacity (in kilobytes)?
    A: df -k

54. Q: How can you edit the contents of a file named master.data?
    A: jot master.data or vi master.data or nedit master.data

55. Q: How can you show the entire contents of a file named master.data on the screen?
    A: cat master.data or more master.data

56. Q: How can you reduce the size of a file named master.data?
    A: compress master.data

57. Q: How can you restore the size & content of a compressed file named master.data.Z?
    A: uncompress master.data.Z

58. Q: What is the file name created by typing compress master.data?
    A: master.data.Z

59. Q: How can you display the 18th and 19th lines of a file named master.data?
    A: head -19 master.data | tail -2

60. Q: How can you print the file named master.data to the default printer for your workstation?
    A: lpr master.data

61. Q: How can you print a file to a particular printer?
    A: type lpr and follow the directions.

62. Q: How can you move all files that end with .psv to a directory named all_psv?
    A: mv *.psv all_psv

63. Q: How can you create a new sub-directory named March.data in a new directory named master.data?
    A: mkdir -p master.data/March.data

64. Q: How can you remove all files named core in your home directory and sub-directories?
    A: find $HOME -name core -exec rm '{}' ';'

65. Q: How can you list all files in your home directory and sub-directories last modified today?
    A: find $HOME -mtime 1 -print

66. Q: How can you list all files in your home directory and sub-directories created more than 4 days ago?
    A: find $HOME -ctime +4 -print

67. Q: How can you determine the location of a command named run.calc that you want to execute?
    A: which run.calc

68. Q: How can you copy a file named current.data to a file named new.data?
    A: cp current.data new.data

69. Q: How can you automatically cont the number of lines that contain the text oregano in a file named spices?
    A: grep oregano spices | wc -l

70. Q: After you ftp a program to your home directory that worked on an identical workstation, can you immediately execute the program?
    A: No. ftp sets all execute permissions to "off".

71. Q: After you copy a program to your home directory that worked on an identical workstation, can you immediately execute the program?
    A: Yes. cp retains all permissions.

72. Q: How can you determine the file type of a file named master.data?
    A: file master.data

73. Q: How can you determine the file type of all files in your current working directory?
    A: file *

74. Q: How can you make a tar image named master.data.tar of a directory named master.data?
    A: tar -cvf master.data.tar master.data

75. Q: How do you restore a tar file named master.data.tar?
    A: tar -xvf master.data.tar

76. Q: How can you list all files and sub-directories that have names that start with zinc_finger?
    A: ls zinc_finger*