parameter to indicate a level of confidence in how well the parame-
ter may be expected to perform. Penalties lower than 10 indicate
the parameter analogy is fair; penalties between 10 and 50 mean
some basic validation of the parameter within the given molecular
context is recommended; penalties higher than 50 indicate poor
analogy and mandate extensive validation and/or optimization.
Validation of force field parameters against experimental data,
such as that from nuclear magnetic resonance or infrared spectros-
copy can confirm their ability to accurately describe the drug mole-
cule in question. In the event that parameters with high penalty
scores are found unsuitable, they can be optimized using tools such
as ffTK [35], which simplifies the workflow required to fit para-
meters to reproduce quantum mechanical descriptions of small
molecules (seeNote 16). For the example system in this chapter,
the parameters generated by ParamChem to describe acetamino-
phen have insignificant penalty scores and may be expected to
accurately reproduce the molecule’s dynamical behavior.4 Project Tutorial
Step 1. Download PDB file of aryl acylamidase–acetaminophen
complex.- Visit the RCSB Protein Data Bank (https://www.rcsb.org) and
search for PDB ID: 4YJI. - From theDownload Filesmenu, selectPDB Formatand save the
file to your working directory (Fig.4).
Step 2. Load PDB file in VMD and visualize the structure.- Launch VMD and load the PDB file by clickingFile!New
Molecule...in theVMD Mainwindow and selecting 4yji.pdb in
theMolecule File Browser(Fig.5). - Open theGraphical Representationswindow by clickingGra-
phics!Representations...in theVMD Mainwindow. - Create a representation of the protein by entering “protein” in
theSelected Atomsfield and choosing NewCartoonfrom the
Drawing Methodmenu. - Create a representation of the drug molecule by entering
“resname TYL” in theSelected Atomsfield and choosingLicorice
from theDrawing Methodmenu. - Create a representation of the crystallographic water molecules
by entering “water” in theSelected Atomsfield and choosing
Licoricefrom theDrawing Methodmenu. - Try creating representations for other structural features of
interest, such as the catalytic triad (“resid 84 163 187”) or
252 Jodi A. Hadden and Juan R. Perilla