(360c) Force Fields Induce Nonplanar Structures for Planar Rings in Some Amino Acids

Molecular modeling of biomolecules uses force fields to describe the intermolecular interactions. Charmm and Amber are two common force fields in biological systems.  Standard implementations of both can lead to some rarely recognized problems that contradict the expected physical structure of some molecules. In this work, Monte Carlo simulations were conducted of a novel antibacterial peptide.  For the Charmm27 force field, initially planar rings on tryptophan and tyrosine repeat units became increasingly nonplanar as the simulations progressed.  Carbon atoms in rings in both units have an SP2 hybridization and thus are typically planar.  It was found that certain angle parameters that correspond to a minimum energy in both these force fields induce these rings to deviate from being in a plane.  Subsequent analysis of other repeat units suggested similar problems can occur for tryptophan and arginine in Amber96.  While recent papers in the literature have developed parameters that address this problem for tryptophan in Charmm, parameters remain unchanged for tyrosine.  A potential impact of these rarely recognized nonplanar structures is inaccuracy in the molecular structures.  Addressing this shortcoming in the force field can enable more precise computational modeling of biological processes to be achieved, which few groups have recognized.