PEPDROID: Development of a Generic DREIDING‐Based Force Field for the Assessment of Peptoid Secondary Structures

Abstract

Abstractα‐Peptoids are peptido‐mimetic foldamers based on poly‐N‐substituted glycines that currently receive a growing interest due to their larger structural diversity, easier synthetic pathways, and larger thermal stability compared to peptides. An appropriate side chain appended to the nitrogen atoms is often crucial to constrain the peptoids into well‐defined and active rigid structures for applications. To shed light on the secondary structure of peptoids, accurate methods for structural characterization are mandatory and typically involve the association of circular dichroism and nuclear magnetic resonance spectroscopies. Molecular simulations can also prove highly complementary to rationalize the relationship between their primary and secondary structures, although much less studies have been reported to date compared to the knowledge accumulated on peptides. To this end, the PEPDROID force field has been developed based on the DREIDING force field, by incorporating a new set of parameters relative to (α and β) peptoids bearing different side chains. The ability of PEPDROID to assess the secondary structure of peptoids by generating Ramachandran‐like plots matching those previously obtained at a quantum‐chemical level for model systems has been demonstrated. For further sake of validation, it is demonstrated that PEPDROID can reproduce the experimental structures of either α‐ or β‐peptoids.

White light emitting silsesquioxane based materials: the importance of a ligand with rigid and directional arms

“…41 A conformational search has then been performed on each molecule to get the most stable structures by coupling molecular mechanics (MM) and molecular dynamics (MD) simulations. All MM/MD calculations have been performed with the Materials Studio (MS) 2018 package using a force field derived from the Dreiding force field, in which (i) the van der Waals radius of the hydrogen atoms has been set to 2.83Å; 42 (ii) the electrostatic term follows Coulomb's law (r-1) instead of the r -2 default potential; (iii) an harmonic constraint (d = 4.82 Å and k = 100 kcal/mol/Ų) has been defined on the distance between the nitrogen atoms of the two terminal pyridine rings of each arm to mimic the presence of a cation; (iv) the octasiloxane core has been geometrically-frozen during all simulations and (v) all the atomic charges have been set to COMPASS atomic charges. The conformational search procedure to extract the most stable structure involves a geometry optimization at the MM level for each molecule followed by successive quenched-MD runs at increasing temperature during which the generated structures are systematically optimized and their energies compared.…”

Engineering the atomic structure of sequence-defined peptoid polymers and their assemblies

“…[73] It is an image processing technique used to improve the resolution of TEM images by analyzing and aligning numerous low signalto-noise ratio images obtained under low-dose conditions. [73] In addition, different force fields, such as PEPDROID [74], MFTOID [63] and CGenFF [75], have been developed to facilitate accurate molecular dynamics (MD) simulations of peptoid structures. Using the feedback between precise synthesis, cryo-7 TEM imaging, and MD simulations, we can now begin to engineer peptoid structures with the same atomic precision that structural biologists use to tune protein structure and function.…”

Organogel Formation Rationalized by Hansen Solubility Parameters: Shift of the Gelation Sphere with the Gelator Structure

“…44 The generated molecular packings were then optimized by molecular mechanics (MM). All of the MM calculations were performed with the Dreiding force field (in which the van der Waals R 0 parameter of the hydrogen atoms with atom type H_ has been reduced from 3.195 to 2.83 Å to properly reproduce van der Waals interactions) 45 and assigning PCFF atomic charges. The best models were then refined using the Reflex module from the Materials Studio software by fitting the experimental XRD pattern using Rietveld refinement coupled with the force field to avoid unrealistic changes in the molecular geometry.…”