Homework #2

ChemBE 414/614
Homework #2
Due: 9/22/2014
1. [20 pts] Workshop #2 Programming Exercise 2. Submit a program called ‘make_helix.py’
and PDB file via GitHub. The program make_helix.py should input an argument to specify
the number of residues in the helix. The program should check that the user has entered a
reasonable value, and if not, give a meaningful error message. Your program must have a
docstring and comply with the PEP8 style guidelines as much as possible. The goal is to
make the code easily readable and understandable. Submit the short answer with the rest of
your homework via Blackboard.
2. [30 pts] Workshop #2 Programming Exercise 4. Name your program
‘ala_ss_propensities.py’ and have it accept a PDB file name as an argument. Again, the
program should have a docstring, check input values, and follow the PEP8 style guidelines.
To test your program, use PDB 1M40 (TEM-1 β-lactamase) to calculate the alanine
propensities. Ten bonus points for each bonus level (‘ss_propensities.py,’ where the
argument can be a PDB file or a text file with a list of PDB files). Submit code and output
via GitHub.
3. [20 pts] Explain briefly how hydrogen bonding, solvation, solvent entropy, and the
hydrophobic effect are related. In a molecular mechanics type approach, which of those
contributions are redundant, and which are independent?
4. Molecular energy calculations. For this problem, download the structure of Cetuximab
bound to the epidermal growth factor receptor (1YY9) from the Protein Data Bank and use
PyMol or PyRosetta to measure any needed distances or other geometric quantities.
a. [5 pts] Identify the closest two heavy-atom pairs between the side chains of
Cetuximab heavy chain residue Y102 and EGFR residue Q408. Use the closest pair
for the following calculations. Use the unbound, separated monomers as your
reference state (i.e., each energy term should become zero if the distance becomes
infinite).
b. [10 pts] Use the Lennard-Jones potential to calculate the van der Waals energy
between the closest two heavy-atoms. Use the polar-hydrogen model of Neria et al.
(CHARMm param19).
c. [10 pts] Use the pair-wise Gaussian exclusion model of Lazaridis & Karplus to
calculate the contribution to the solvation potential energy between the closest two
heavy-atoms. Explain why the sign of the energy is positive or negative.
d. [10 pts] Use the statistical potential of Kortemme et al. to calculate a hydrogen bond
energy between the same two side chains. Use PyMol’s “h_add” function to place
the hydrogen atoms, or read and write the structure from PyRosetta to have it place
the hydrogens.
ChemBE 616 additional questions:
1. How does the H placement affect your calculation?
2. How does PyMol or PyRosetta place the H?
3. What do you think the best way to place the H might be?
e. [10 pts] Which type of energy contributes most to the Y102-Q408 interaction, van der
Waals, solvation or hydrogen bonding? Is this a valid question? What is the
reference state?

Download Report