Development of a Pantetheine Force Field Library for Molecular Modeling.

Pantetheine is ubiquitous in nature in various forms of pantetheine-containing ligands (PCLs), including coenzyme A and phosphopantetheine. Lack of scalable force field libraries for PCLs has hampered the computational studies of biological macromolecules containing PCLs. We describe here the development of the first generation Pantetheine Force Field (PFF) library that is compatible with Amber force fields; parameterized using Gasteiger, AM1-BCC, or RESP charging methods combined with gaff2 and ff14SB parameter sets. In addition, a "plug-and-play" strategy was employed to enable the systematic charging of computationally expensive molecules sharing common substructural motifs. The validation studies performed on the PFF library showed promising performance where molecular dynamics (MD) simulations results were compared with experimental data of three representative systems. The PFF library represents the first force field library capable of modeling systems containing PCLs in silico and will aid in various applications including protein engineering and drug discovery.