We present a new force field, AMBER ff15ipq-m, for simulations of protein mimetics in applications from therapeutics to biomaterials. This force field is an expansion of the AMBER ff15ipq force field that was developed for canonical proteins and enables the modeling of four classes of artificial backbone units that are commonly used alongside natural α residues in blended or “heterogeneous” backbones: chirality-reversed D-α-residues, the Cα-methylated α-residue Aib, homologated β-residues (β3) bearing proteinogenic side chains, and two cyclic β residues (βcyc; APC and ACPC). The ff15ipq-m force field includes 472 unique atomic charges and 148 unique torsion terms. Consistent with the AMBER IPolQ lineage of force fields, the charges were derived using the Implicitly Polarized Charge (IPolQ) scheme in the presence of explicit solvent. To our knowledge, no general force field reported to date models the combination of artificial building blocks examined here. In addition, we have derived Karplus coefficients for the calculation of backbone amide J-coupling constants for β3Ala and ACPC β residues. The AMBER ff15ipq-m force field reproduces experimentally observed J-coupling constants in simple tetrapeptides and maintains the expected conformational propensities in reported structures of proteins/peptides containing the artificial building blocks of interest—all on the μs timescale. These encouraging results demonstrate the power and robustness of the IPolQ lineage of force fields in modeling the structure and dynamics of natural proteins as well as mimetics with protein-inspired artificial backbones in atomic detail.
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14 August 2020
Research Article|
August 10 2020
A twist in the road less traveled: The AMBER ff15ipq-m force field for protein mimetics
Anthony T. Bogetti
;
Anthony T. Bogetti
1
Department of Chemistry, University of Pittsburgh
, Pittsburgh, Pennsylvania 15260, USA
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Hannah E. Piston
;
Hannah E. Piston
1
Department of Chemistry, University of Pittsburgh
, Pittsburgh, Pennsylvania 15260, USA
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Jeremy M. G. Leung
;
Jeremy M. G. Leung
1
Department of Chemistry, University of Pittsburgh
, Pittsburgh, Pennsylvania 15260, USA
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Chino C. Cabalteja
;
Chino C. Cabalteja
1
Department of Chemistry, University of Pittsburgh
, Pittsburgh, Pennsylvania 15260, USA
2
Molecular Biophysics and Structural Biology Graduate Program, University of Pittsburgh and Carnegie Mellon University
, Pittsburgh, Pennsylvania 15260, USA
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Darian T. Yang
;
Darian T. Yang
2
Molecular Biophysics and Structural Biology Graduate Program, University of Pittsburgh and Carnegie Mellon University
, Pittsburgh, Pennsylvania 15260, USA
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Alex J. DeGrave
;
Alex J. DeGrave
3
School of Computer Science and Engineering, University of Washington
, Seattle, Washington 98115, USA
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Karl T. Debiec
;
Karl T. Debiec
1
Department of Chemistry, University of Pittsburgh
, Pittsburgh, Pennsylvania 15260, USA
2
Molecular Biophysics and Structural Biology Graduate Program, University of Pittsburgh and Carnegie Mellon University
, Pittsburgh, Pennsylvania 15260, USA
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David S. Cerutti
;
David S. Cerutti
4
Department of Chemistry and Chemical Biology, Rutgers University
, New Brunswick, New Jersey 008854, USA
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David A. Case
;
David A. Case
4
Department of Chemistry and Chemical Biology, Rutgers University
, New Brunswick, New Jersey 008854, USA
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W. Seth Horne
;
W. Seth Horne
a)
1
Department of Chemistry, University of Pittsburgh
, Pittsburgh, Pennsylvania 15260, USA
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Lillian T. Chong
Lillian T. Chong
a)
1
Department of Chemistry, University of Pittsburgh
, Pittsburgh, Pennsylvania 15260, USA
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Note: This paper is part of the JCP Special Topic on Classical Molecular Dynamics (MD) Simulations: Codes, Algorithms, Force Fields, and Applications.
J. Chem. Phys. 153, 064101 (2020)
Article history
Received:
June 19 2020
Accepted:
July 19 2020
Citation
Anthony T. Bogetti, Hannah E. Piston, Jeremy M. G. Leung, Chino C. Cabalteja, Darian T. Yang, Alex J. DeGrave, Karl T. Debiec, David S. Cerutti, David A. Case, W. Seth Horne, Lillian T. Chong; A twist in the road less traveled: The AMBER ff15ipq-m force field for protein mimetics. J. Chem. Phys. 14 August 2020; 153 (6): 064101. https://doi.org/10.1063/5.0019054
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