Pyranose Ring Puckering Thermodynamics for Glycan Monosaccharides Associated with Vertebrate Proteins

The conformational properties of carbohydrates can contribute to protein structure directly through covalent conjugation in the cases of glycoproteins and proteoglycans and indirectly in the case of transmembrane proteins embedded in glycolipid-containing bilayers. However, there continue to be significant challenges associated with experimental structural biology of such carbohydrate-containing systems. All-atom explicit-solvent molecular dynamics simulations provide a direct atomic resolution view of biomolecular dynamics and thermodynamics, but the accuracy of the results depends on the quality of the force field parametrization used in the simulations. A key determinant of the conformational properties of carbohydrates is ring puckering. Here, we applied extended system adaptive biasing force (eABF) all-atom explicit-solvent molecular dynamics simulations to characterize the ring puckering thermodynamics of the ten common pyranose monosaccharides found in vertebrate biology (as represented by the CHARMM carbohydrate force field). The results, along with those for idose, demonstrate that the CHARMM force field reliably models ring puckering across this diverse set of molecules, including accurately capturing the subtle balance between 4C1 and 1C4 chair conformations in the cases of iduronate and of idose. This suggests the broad applicability of the force field for accurate modeling of carbohydrate-containing vertebrate biomolecules such as glycoproteins, proteoglycans, and glycolipids.

Spectroscopic and Theoretical Study of the Intramolecular π-Type Hydrogen Bonding and Conformations of 2-Cyclopenten-1-ol

The conformations of 2-cyclopenten-1-ol (2CPOL) have been investigated by high-level theoretical computations and infrared spectroscopy. The six conformational minima correspond to specific values of the ring-puckering and OH internal rotation coordinates. The conformation with the lowest energy possesses intramolecular π-type hydrogen bonding. A second conformer with weaker hydrogen bonding has somewhat higher energy. Ab initio coupled-cluster theory with single and double excitations (CCSD) was used with the cc-pVTZ (triple-ζ) basis set to calculate the two-dimensional potential energy surface (PES) governing the conformational dynamics along the ring-puckering and internal rotation coordinates. The two conformers with the hydrogen bonding lie about 300 cm−1 (0.8 kcal/mole) lower in energy than the other four conformers. The lowest energy conformation has a calculated distance of 2.68 Å from the hydrogen atom on the OH group to the middle of the C=C double bond. For the other conformers, this distance is at least 0.3 Å longer. The infrared spectrum in the O-H stretching region agrees well with the predicted frequency differences between the conformers and shows the conformers with the hydrogen bonding to have the lowest values. The infrared spectra in other regions arise mostly from the two hydrogen-bonded species.

Nonradiative relaxation mechanisms of the elusive silole molecule

The relaxation of excited-state silole was studied using XMS-CASPT2 and ADC(2) static and dynamic calculations, with ring puckering playing a major role.

Understanding Ring Puckering in Small Molecules and Cyclic Peptides

<div>The geometry of a molecule plays a significant role in determining its physical and chemical properties. Despite its importance, there are relatively few studies on ring puckering and conformations, often focused on small cycloalkanes, five- and six-membered carbohydrate rings and specific macrocycle families. We lack a general understanding of the puckering preferences of medium-sized rings and macrocycles. To address this, we provide an extensive conformational analysis of a diverse set of rings. We used Cremer-Pople puckering coordinates to study the trends of the ring conformation across a set of 140,000 diverse small molecules, including small rings, macrocycles and cyclic peptides. By standardizing using key atoms, we show that the ring conformations can be classified into relatively few conformational clusters, based on their canonical forms. The number of such canonical clusters increases slowly with ring size. Ring puckering motions, especially pseudo-rotations, are generally restricted, and differ between clusters. More importantly, we propose models to map puckering preferences to torsion space, which allows us to understand the interrelated changes in torsion angles during pseudo-rotation and other puckering motions. Beyond ring puckers, our models also explain the change in substituent orientation upon puckering. In summary, this work provides an improved understanding of general ring puckering preferences, which will in turn accelerate the identification of low energy ring conformations for applications from polymeric materials to drug binding.</div>

Understanding Ring Puckering in Small Molecules and Cyclic Peptides

<div>The geometry of a molecule plays a significant role in determining its physical and chemical properties. Despite its importance, there are relatively few studies on ring puckering and conformations, often focused on small cycloalkanes, five- and six-membered carbohydrate rings and specific macrocycle families. We lack a general understanding of the puckering preferences of medium-sized rings and macrocycles. To address this, we provide an extensive conformational analysis of a diverse set of rings. We used Cremer-Pople puckering coordinates to study the trends of the ring conformation across a set of 140,000 diverse small molecules, including small rings, macrocycles and cyclic peptides. By standardizing using key atoms, we show that the ring conformations can be classified into relatively few conformational clusters, based on their canonical forms. The number of such canonical clusters increases slowly with ring size. Ring puckering motions, especially pseudo-rotations, are generally restricted, and differ between clusters. More importantly, we propose models to map puckering preferences to torsion space, which allows us to understand the interrelated changes in torsion angles during pseudo-rotation and other puckering motions. Beyond ring puckers, our models also explain the change in substituent orientation upon puckering. In summary, this work provides an improved understanding of general ring puckering preferences, which will in turn accelerate the identification of low energy ring conformations for applications from polymeric materials to drug binding.</div>