"Azide and Alkyne CHARMM Parameterization with the Force Field took kit (ffTK) and Unnatural Amino Acid (uAA) Protein Simulation"

Drug-like small molecules that contain azido and akynyl groups are structurally unique because they contain linear angles useful in therapeutics and bioconjugation reactions. The bioconjugation "click" reactions has been useful in drug design and uAA research; however, these technologies rely heavily on molecular modeling.

CGenFF and CHARMM are common force fields for drug-like molecules; however, this force field lacks parameters for linearangle molecular moieties and current literature does not contain any solution. We propose a method that (1) develops CHARMM parameters for four small molecules that contain terminal azido and alkynyl groups using ffTK, (2) addresses linearity issues, and (3) validates ffTK results via in silico MD simulation. We then combine these parameters with CGenFF to generate parameters for uAA MD simulation.

In this presentation we prove that the physics of the linear terminal dihedral angles are well-represented by multiple parameter sets as long as they maintain the linear structures. We then show the reliability of our parameter set by running MD simulations to prove our modeled structures match those found in literature and quantum theory. Finally, protein MD compares simulation with crystallographic data using a protein that contains an azide uAA.