Physicochemical properties of poly-L-lysine (PLL) hydrobromide were determined by Molecular Dynamics (MD) modeling and a variety of experimental techniques. Primarily, the density, the chain diameter, the monomer length and PLL molecule conformations were theoretically calculated. These results were applied for the interpretation of experimental data acquired for 2 PLL sample of the average molar mass equal to 122 kg/mol. They comprised the diffusion coefficient, the hydrodynamic diameter and the electrophoretic mobility of molecules determined for ionic strength range 2×10 -5 to 0.15 M and pH 5.6. Using these data, the electrokinetic charge and the effective ionization degree of PLL molecules were determined as a function of ionic strength. Additionally, precise dynamic viscosity measurements for dilute PLL solutions were performed yielding the intrinsic viscosity, which decreased from 2420 to 120, for ionic strength of 2×10 -5 and 0.15 M, respectively. This confirmed that PLL molecules assume extended conformations in accordance with theoretical modeling. These data enabled to determine the molecule length, the chain diameter and its effective molecule cross-section area for various ionic strengths. Therefore, it was concluded that the combined dynamic light scattering and viscosity measurements supplemented by MD modeling furnish reliable information about PLL macromolecule conformations in electrolyte solution. Beside significance for basic science, the results obtained in this work can be exploited for precisely determining molar mass of macroions.

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Microsecond-long all-atom molecular dynamics (MD) simulations, circular dichroism, laser Doppler velocimetry, and dynamic light-scattering techniques have been used to investigate pH-induced changes in the secondary structure, charge, and conformation of poly l -lysine (PLL) and poly l -glutamic acid (PGA). The employed combination of the experimental methods reveals for both PLL and PGA a narrow pH range at which they are charged enough to form stable colloidal suspensions, maintaining their α-helix content above 60%; an elevated charge state of the peptides required for colloidal stability promotes the peptide solvation as a random coil. To obtain a more microscopic view on the conformations and to verify the modeling performance, peptide secondary structure and conformations rising in MD simulations are also examined using three different force fields, i.e., OPLS-AA, CHARMM27, and AMBER99SB*-ILDNP. Ramachandran plots reveal that in the examined setup the α-helix content is systematically overestimated in CHARMM27, while OPLS-AA overestimates the β-sheet fraction at lower ionization degrees. At high ionization degrees, the OPLS-AA force-field-predicted secondary structure fractions match the experimentally measured distribution most closely. However, the pH-induced changes in PLL and PGA secondary structure are reasonably captured only by the AMBER99SB*-ILDNP force field, with the exception of the fully charged PGA in which the α-helix content is overestimated. The comparison to simulations results shows that the examined force fields involve significant deviations in their predictions for charged homopolypeptides. The detailed mapping of secondary structure dependency on pH for the polypeptides, especially finding the stable colloidal α-helical regime for both examined peptides, has significant potential for practical applications of the charged homopolypeptides. The findings raise attention especially to the pH fine tuning as an underappreciated control factor in surface modification and self-assembly.

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