Oxoanion Binding by Guanidiniocarbonylpyrrole Cations in Water: A Combined DFT and MD Investigation

Abstract

Structures and properties of nonbonding interactions involving guanidinium-functionalized hosts and carboxylate substrates were investigated by a combination of ab initio and molecular dynamics approaches. The systems under study are on one hand intended to be a model of the arginine-anion bond, so often observed in proteins and nucleic acids, and on the other to provide an opportunity to investigate the influence of molecular structure on the formation of supramolecular complexes in detail. Use of DFT calculations, including extended basis sets and implicit water treatment, allowed us to determine minimum-energy structures and binding enthalpies that compared well with experimental data. Intermolecular forces were found to be mostly due to electrostatic interactions through three hydrogen bonds, one of which is bifurcate, and are sufficiently strong to induce a conformational change in the ligand consisting of a rotation of about 180 degrees around the guanidiniocarbonylpyrrole axis. Free binding energies of the complexes were evaluated through MD simulations performed in the presence of explicit water molecules by use of the molecular mechanics Poisson-Boltzmann solvent accessible surface area (MM-PBSA) and linear interaction energy (LIE) approaches. LIE energies were in quantitative agreement with experimental data. A detailed analysis of the MD simulations revealed that the complexes cannot be described in terms of a single binding structure, but that they are characterized by a significant internal mobility responsible for several low-energy metastable structures.

A Journey through 12 Years of Interacting Molecules: From Artificial Amino Acid Receptors to the Recognition of Biomolecules and Switchable [nl]Nanomaterials

“…Several years later, these findings were backed up by high-level density functional theory (DFT) calculations ( Figure 6). 18 The calculations not only confirmed the prime conclusions, but also led to a modification of the initially proposed binding mode for amino acid carboxylates. According to the DFT calculations, it is energetically too costly for all NHs of the receptor to point inwards as needed for the ini- Figure 6 Comparison between the initially proposed binding mode and the one obtained from high-level density functional theory calculations (MD simulations with explicit solvent), and the CPK model of the energy-minimized structure of the complex involving N-Ac-L-Ala tially proposed binding mode.…”

Molecular modeling to rationalize ligand–support interactions in affinity chromatography

“…This parameter can in fact predict the tendency of a given spacer-ligand adduct of being solvated by a polar solvent -such as water -versus its hydrophobicity and it is directly related to Eq. (5), as it is known that solvation free energies and SAA are linearly correlated (see the discussion on linear interaction energy in Moiani et al [44]). r sol is reported in Fig.…”

Targeting Allostery with Avatars to Design Inhibitors Assessed by Cell Activity: Dissecting MRE11 Endo- and Exonuclease Activities

“…In this approach, the in silico characterization is completed with a computational energy evaluation for implicit or explicit solvation models that can be calculated and efficiently compared with calorimetric experimental data (Moiani, Cavallotti, Famulari, & Schmuck, 2008). The best candidate is thereby identified for additional in vitro experiments, such as biophysical characterizations, and for testing in several cell lines.…”