Molecular modeling study of adsorption of poly-L-lysine onto silica glass

Abstract

A research program was initiated with both experimental and computational chemistry based molecular modeling components to investigate specific amino acid-surface interactions. The experimental portion of this study, with details reported elsewhere, investigated the adsorption of selected molecular weights of poly(L-lysine) onto silica glass microspheres with the adsorption enthalpy per adsorbed mer determined to be -0.23 +/- 0.13 kcal/mol (mean +/- 95% confidence interval). Molecular modeling of this system was then conducted using two approaches: an AM1 semiempirical molecular orbital method to predict L-lysine/glass interaction energy and an MM2 molecular mechanics method to investigate the structural configuration for poly(L-lysine). The modeling predicted a minimum energy configuration of a rotational backbone structure for poly(L-lysine) with approximately one full rotation occurring about every 8 mers, and that the amine side chains of the L-lysine will hydrogen bond with the silica surface with an average adsorption energy of approximately -0.34 kcal/mol/mer. The molecular modeling results are in good agreement with the experimentally measured value and provide insights into possible molecular-level behavior which would be very difficult to determine by experimental analyses alone. This work demonstrates the use of molecular modeling in conjunction with experimental studies to investigate complex molecular interactions.

Theoretical analysis of adsorption thermodynamics for charged peptide residues on SAM surfaces of varying functionality

“…Molecular modeling is a powerful tool that can enable the complex processes of protein adsorption on a submolecular level to be addressed. The theoretical study presented herein builds on previously reported modeling and experimental studies by Latour and coworkers,40–42 which address the thermodynamic contributions of the adsorption of mid‐chain peptide residues to synthetic surfaces. Currently, experimental studies are being conducted in attempt to verify the findings of this present study.…”

Low-fouling, mixed-charge poly-l-lysine polymers with anionic oligopeptide side-chains

“…35 Poly-L-lysine (PLL) is a versatile polymer, composed of positively charged lysine amino acid as a repeat unit, which has attractive biochemical properties, including hydrophilicity, excellent biocompatibility and an acceptable degree of biodegradability. Because PLL is positively charged at physiological pH, it can be easily adsorbed on a large variety of negatively charged substrates via electrostatic interactions, including glass, 36 metals, 37 polymers, 38 and metallic oxides. 39 Furthermore, PLL polymers can be easily modified with nonionic side-chains (like PEG/OEG), thereby making it an ideal candidate for engineering biomaterial interfaces, such as surface coatings, 37,40 drug, 41 gene, 42 and protein 43 delivery platforms, and hydrogel scaffolds.…”

Are AM1 ligand‐protein binding enthalpies good enough for use in the rational design of new drugs?

“…The affinity of a ligand for its receptor can also be evaluated by means of semiempirical QM methods,7–11 such as AM112 or PM3,13 which allow the physico‐chemical properties of medium‐sized and large systems to be investigated with a reasonable computational cost. In spite of the known limitations of semiempirical methods based on the neglect diatomic differential overlap (NDDO) approximation,14–16 they continue to find use in different applications such as the prediction of specific surface interactions on silica17 or carbon nanotubes,18 the qualitative interpretation of ligand‐protein19 interactions, and the estimation of the solvation contribution20 in those kinds of interactions. One of the problems associated with NDDO‐based methods is that they do not reproduce hydrogen bonding with good accuracy.…”