Molecular Dynamics Studies of Atomistically Determined Fibrillar Assemblies: Comparison of the Rippled β-Sheet, Pleated β-Sheet, and Herringbone Structures
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1.
California Institute of Technology
Abstract
Pauling and Corey expected that a racemic mixture would result in a rippled β-sheet, however, it has been known from experiments that the racemic mixtures of triphenylalanine lead to a herringbone structure. Because of the theoretical limitations concerning crystal structures such as rippled β-sheet, it is inevitable to understand how the interplay of the amino acids prefers a specific structural motif. In this paper we use molecular dynamics to understand the sequence- and enantiomer-dependent structures by comparisons between rippled β-sheet and pleated β-sheet, solvated and anhydrous rippled β-sheet, and rippled β-sheet and the herringbone structure, based on thermodynamics and structures at the atomic level. The tripeptides select the favored structure that can be stabilized through aromatic or hydrogen bonding interactions between tripeptides. Furthermore, the solubility is determined by the environment of space that is created around the side chains. Our findings provide comprehensive insight into the crystallized fibril motif of the polypeptide.
Copyright and License
© 2024 American Chemical Society.
Acknowledgement
WAG thanks the US NSF (CBET 2311117) for support. JAR thanks the NIH for the award R01AG074954 and the Seaver Institute for a generous gift. Prof. Harry B. Gray is gratefully acknowledged for helpful discussions.
Data Availability
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Figure S1 shows the initial unit cell obtained from X-ray crystallography. Figure S2 shows the change of the force applied to the systems during NPT MD simulation. Figure S3 shows the change in RMSD of systems obtained from X-ray crystallography. Figure S4 shows representative MD snapshots of anhydrous [FYF:fyf]n and [fyf:fyf]n. Figure S5 shows the optimized FYF, fyf, FFF, and fff configurations with potential energy. Figure S6 shows the Enb between BB-BB and SC-SC in the solvated [FYF:fyf]n and [FYF:FYF]n. Figure S7 shows the probability of finding water molecules and the projected snapshot of solvated [FYF:fyf]n. Figure S8 shows the 8 tripeptides of [FFF:fff]n with several HBs between backbones and parallel displacement aromatic interaction among the benzene rings. Table S1 summarizes the number of peptides, water molecules, and atoms for all systems. Table S2 compares the lattice parameters of the supercell obtained from X-ray crystallography and the equilibrium lattice parameters from MD simulation. Table S3 compares the diffusion coefficients of BB and SC in solvated [FYF:fyf]n and [FYF:FYF]n. Table S4 lists the number of HB interactions in solvated [FYF:fyf]n and [FYF:FYF]n. Table S5 shows the CED values for [FFF:fff]n and anhydrous [FYF:fyf]n with a herringbone structure and rippled β-sheet structure. (PDF)
Conflict of Interest
The authors declare no competing financial interest.
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Additional details
- ISSN
- 1948-7185
- National Science Foundation
- CBET-2311117
- National Institutes of Health
- R01AG074954