NCAP: Noncanonical\nAmino Acid Parameterization Software\nfor CHARMM Potentials

Noncanonical amino acids (ncAAs) provide numerous avenues\nfor the\nintroduction of novel functionality to peptides and proteins. ncAAs\ncan be incorporated through solid-phase synthesis or genetic code\nexpansion in conjugation with heterologous expression of the encoded\nprotein modification. Due to the difficulty of synthesis or overexpression,\nwide chemical space, and lack of empirically resolved structures,\nmodeling the effects of ncAA mutation is critical for rational protein\ndesign. To evaluate the structural and functional perturbations ncAAs\nintroduce, we utilize molecular potentials that describe the forces\nin the protein structure. Most potentials such as CHARMM are designed\nto model canonical residues but can be parametrized to include novel\nncAAs. In this work, we introduce NCAP, a software package to generate\nCHARMM-compatible parameters from quantum chemical calculations. Unlike\ncurrently available tools, NCAP is designed to recognize the ncAA\nstructure and automatically bridge the gap between quantum chemical\ncalculations and CHARMM potential parameters. For our software, we\ndiscuss the workflow, validation against canonical parameter sets,\nand comparison with published ncAA-protein structures.