title: Further along the Road Less Traveled: AMBER ff15ipq, an Original Protein Force Field Built on a Self-Consistent Physical Model.
abstract: We present the AMBER ff15ipq force field for proteins, the second-generation force field developed using the Implicitly Polarized Q (IPolQ) scheme for deriving implicitly polarized atomic charges in the presence of explicit solvent. The ff15ipq force field is a complete rederivation including more than 300 unique atomic charges, 900 unique torsion terms, 60 new angle parameters, and new atomic radii for polar hydrogens. The atomic charges were derived in the context of the SPC/Eb water model, which yields more-accurate rotational diffusion of proteins and enables direct calculation of nuclear magnetic resonance (NMR) relaxation parameters from molecular dynamics simulations. The atomic radii improve the accuracy of modeling salt bridge interactions relative to contemporary fixed-charge force fields, rectifying a limitation of ff14ipq that resulted from its use of pair-specific Lennard-Jones radii. In addition, ff15ipq reproduces penta-alanine J-coupling constants exceptionally well, gives reasonable agreement with NMR relaxation rates, and maintains the expected conformational propensities of structured proteins/peptides, as well as disordered peptides-all on the microsecond (μs) time scale, which is a critical regime for drug design applications. These encouraging results demonstrate the power and robustness of our automated methods for deriving new force fields. All parameters described here and the mdgx program used to fit them are included in the AmberTools16 distribution.
authors.affiliation: Molecular Biophysics and Structural Biology Graduate Program, University of Pittsburgh and Carnegie Mellon University , Pittsburgh, Pennsylvania, United States.|Department of Structural Biology, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania 15260, United States.|Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Karl T
authors.initials: KT
authors.lastname: Debiec
authors.affiliation: Department of Chemistry, Michigan State University , East Lansing, Michigan 48824, United States.
authors.forename: David S
authors.initials: DS
authors.lastname: Cerutti
authors.affiliation: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Lewis R
authors.initials: LR
authors.lastname: Baker
authors.affiliation: Department of Structural Biology, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Gronenborn
authors.affiliation: Department of Chemistry and Chemical Biology, Rutgers University , New Brunswick, New Jersey 08854, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Case
authors.affiliation: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Lillian T
authors.initials: LT
authors.lastname: Chong