Abstract
A new modification to the AMBER force field that incorporates the coupled two-dimensional main chain torsion energy has been evaluated for the balanced representation of secondary structures. In this modified AMBER force field (AMBER032D), the main chain torsion energy is represented by 2-dimensional Fourier expansions with parameters fitted to the potential energy surface generated by high-level quantum mechanical calculations of small peptides in solution. Molecular dynamics simulations are performed to study the folding of two model peptides adopting either α-helix or β-hairpin structures. Both peptides are successfully folded into their native structures using an AMBER032D force field with the implementation of a polarization scheme (AMBER032Dp). For comparison, simulations using a standard AMBER03 force field with and without polarization, as well as AMBER032D without polarization, fail to fold both peptides successfully. The correction to secondary structure propensity in the AMBER03 force field and the polarization effect are critical to folding Trpzip2; without these factors, a helical structure is obtained. This study strongly suggests that this new force field is capable of providing a more balanced preference for helical and extended conformations. The electrostatic polarization effect is shown to be indispensable to the growth of secondary structures.
Highlights
Unraveling the mechanism of protein folding has been a grand challenge in biological science for decades[1,2,3]
We evaluate the quality of AMBER032D and AMBER99SB2D force fields for 19 amino acids using molecular simulations and compare these results with those of AMBER03 and AMBER99SB force fields
After the 2D torsional potential correction, the secondary structural populations for AMBER032D and AMBER99SB2D force fields are nearly the same, which indicates the well-balanced character of these 2D force fields
Summary
Unraveling the mechanism of protein folding has been a grand challenge in biological science for decades[1,2,3]. Best et al calibrated the backbone rotation terms in the widely used AMBER03, AMBER99SB, and CHARMM22/ CMAP force fields, which resulted in a significant improvement in reproducing experimental residual www.nature.com/scientificreports/. We calibrated the AMBER03 and AMBER99SB force fields by replacing the one-dimensional Fourier series for φ and ψ with a coupled 2-dimensional (2D) main chain torsion energy (denoted AMBER032D and AMBER99SB2D)[39]. These two force fields are more balanced among various conformations than the original AMBER force fields. The AMBER03 force field is too helical to fold the β -hairpin peptide whether the polarization effect is included or excluded
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