Exercises for Chapter 7 – Characterization via Charges
Overview: The practical exercises will be performed using the software tool Atom
icChargeCalculator (ACC), because it provides both charge calculation and visual
ization, and is currently the only available web application for charge calculation. A
usage of the ACC is shown in the solution of demo exercise 1 and also in the ACC
manual.
1. Demo exercise: Detection of the first dissociating hydrogen in 3-hydroxybenzoic acid
3-hydroxybenzoic acid contains two hydrogens, which can potentially dissoci
ate. The hydrogen from the COOH group and the hydrogen from the OH group.
The more positively charged hydrogen will dissociate first. Calculate atomic
charges for the 3-hydroxybenzoic acid using ACC (with Bult2002 mpa para
meters) and detect the first dissociating hydrogen.
2. Comparison of charges in phenol molecules and detection of correlationbetween charges and pKa.
Download from PubChem the 3D structures of the molecules mentioned in
the table below. For all the molecules calculate partial atomic charges using
ACC (with Bult2002 mpa parameters). Analyze, if there is any dependency
between the pKa of the molecules and the atomic charges of certain atoms. Spe
cifically, focus on charges on the H and O from the phenolic OH group, the C
connected to the OH group and the charges on the C atoms in the phenolic ring.
Molecule Pubchem ID pKa
2,4,6-trinitrophenol 6954 0.38
2,3-dinitrophenol 6191 5.96
3-hydroxybenzaldehyde 101 8.5
2,4,6-trimethylphenol 10698 10.9
3. Comparison of charge distributions in cocaine binding sites
Calculate partial atomic charges for two cocaine (PDB residue ID COC) antibod
ies, specifically Anti-Cocaine Antibody M82G2 (PDB ID 1q72) and Cocaine
catalytic Antibody 7A1 Fab’ (PDB ID 2ajv). Afterwards, compare charge dis
tribution in cocaine binding sites. Note: In both cases, delete water and cocaine
molecules before starting the charge calculation. Use ACC with default settings
for the calculation. Visualize the charge distribution in ACC using the Display
Mode Surface and Probe Radius 1.4.
4. Comparison of a charge distribution in activated and inhibited apoptoticproteins
BAX is a protein participating in regulation of apoptosis – programmed cell
death. When the cell is healthy, BAX is inactive and its C domain is tightly
bound to its structure (see the figure below). During apoptosis, BAX is activated
(i.e., an activator is bound to the activation site), its C domain becomes free, can
insert into the mitochondrial membrane and penetrate it. It was found [8] that
the activation is realized via a charge transfer and that helices 1 and 5 (see
Figure 7.3) play a role in this process. In this exercise, you will compare the
charge distribution in active and inhibited BAX.
Calculate charges in inactive BAX (PDB ID 1f16), inactive BAX in complex
with its inhibitor (PDB ID 2lr1) and active BAX (PDB ID 2k7w) via ACC.
Describe how the charges in helix 1, helix 5 and the C domain changed.
