Forcefield_PTM:Ab InitioCharge and AMBER Forcefield Parameters for Frequently Occurring Post-Translational Modifications

Citations Over TimeTop 10% of 2013 papers

Abstract

In this work, we introduce Forcefield_PTM, a set of AMBER forcefield parameters consistent with ff03 for 32 common post-translational modifications. Partial charges were calculated through ab initio calculations and a two-stage RESP-fitting procedure in an ether-like implicit solvent environment. The charges were found to be generally consistent with others previously reported for phosphorylated amino acids, and trimethyllysine, using different parameterization methods. Pairs of modified and their corresponding unmodified structures were curated from the PDB for both single and multiple modifications. Background structural similarity was assessed in the context of secondary and tertiary structures from the global dataset. Next, the charges derived for Forcefield_PTM were tested on a macroscopic scale using unrestrained all-atom Langevin molecular dynamics simulations in AMBER for 34 (17 pairs of modified/unmodified) systems in implicit solvent. Assessment was performed in the context of secondary structure preservation, stability in energies, and correlations between the modified and unmodified structure trajectories on the aggregate. As an illustration of their utility, the parameters were used to compare the structural stability of the phosphorylated and dephosphorylated forms of OdhI. Microscopic comparisons between quantum and AMBER single point energies along key χ torsions on several PTMs were performed and corrections to improve their agreement in terms of mean squared errors and squared correlation coefficients were parameterized. This forcefield for post-translational modifications in condensed-phase simulations can be applied to a number of biologically relevant and timely applications including protein structure prediction, protein and peptide design, docking, and to study the effect of PTMs on folding and dynamics. We make the derived parameters and an associated interactive webtool capable of performing post-translational modifications on proteins using Forcefield_PTM available at http://selene.princeton.edu/FFPTM.

Related Papers

• → Ab initio quantum-chemical study of the unimolecular pyrolysis mechanisms of acetic acid(1986)32 cited
• → Methanediol decomposition mechanisms: A study considering various ab initio approaches(1996)18 cited
• → ESR study and ab initio calculations of some methylbenzoates derivatives.(1986)4 cited
• → The oximes of cyclopropenone, cyclopropanone and acetone and their O- and N-protonated forms. An ab initio and semiempirical quantum chemical study(1993)1 cited
• → $\textit{Ab initio}$ study of highly tunable charge transfer in $β$-RuCl$_3$/graphene heterostructures(2024)