A new derivation of the GLYCAM06 force field, which removes its previous specificity for carbohydrates, and its dependency on the AMBER force field and parameters, is presented. All pertinent force field terms have been explicitly specified and so no default or generic parameters are employed. The new GLYCAM is no longer limited to any particular class of biomolecules, but is extendible to all molecular classes in the spirit of a small-molecule force field. The torsion terms in the present work were all derived from quantum mechanical data from a collection of minimal molecular fragments and related small molecules. For carbohydrates, there is now a single parameter set applicable to both alpha- and beta-anomers and to all monosaccharide ring sizes and conformations. We demonstrate that deriving dihedral parameters by fitting to QM data for internal rotational energy curves for representative small molecules generally leads to correct rotamer populations in molecular dynamics simulations, and that this approach removes the need for phase corrections in the dihedral terms. However, we note that there are cases where this approach is inadequate. Reported here are the basic components of the new force field as well as an illustration of its extension to carbohydrates. In addition to reproducing the gas-phase properties of an array of small test molecules, condensed-phase simulations employing GLYCAM06 are shown to reproduce rotamer populations for key small molecules and representative biopolymer building blocks in explicit water, as well as crystalline lattice properties, such as unit cell dimensions, and vibrational frequencies.

/pdf/glycam06-a-generalizable-biomolecular-force-field-2f07t7094q.pdf

GLYCAM06: a generalizable biomolecular force field. Carbohydrates.

Experiential phenomena occurring in spontaneous seizures or evoked by brain stimulation were reported by 18 of 29 patients with medically intractable temporal lobe epilepsy who were investigated with chronic, stereotaxically implanted intracerebral electrodes. The phenomena mainly consisted of perceptual (visual or auditory) hallucinations or illusions, memory flashbacks, illusions of familiarity, forced thinking, or emotions. Experiential phenomena did not occur unless a seizure discharge or electrical stimulation involved limbic structures. For such phenomena to occur, seizure discharge or electrical stimulation did not have to implicate temporal neocortex. This was true even for perceptual experiential phenomena. Many experiential responses elicited by electrical stimulation, particularly when applied to the amygdala, were not associated with electrical afterdischarge. Limbic activation by seizure discharge or electrical stimulation may add an affective dimension to perceptual and mnemonic data processed by the temporal neocortex, which may be required for endowing them with experiential immediacy.

The role of the limbic system in experiential phenomena of temporal lobe epilepsy

The relationship between the three-dimensional structures of oligosaccharides and polysaccharides and their biological properties has been the focus of many recent studies. The overall conformation of an oligosaccharide depends primarily on the orientation of the torsion angles (φ, ψ, and ω) between glycosyl residues. Numerous experimental studies have shown that in glucopyranosides the ω-torsion angle (O6-C6-C5-O5) displays a preference for gauche orientations, in disagreement with predictions based on gas-phase quantum mechanics calculations. In contrast, the ω-angle in galactopyranosides displays a high proportion of the anti-orientation. For oligosaccharides containing glycosidic linkages at the 6-position (1→6 linked), variations in rotamer population have a direct effect on the oligosaccharides' structure and function, and yet the physical origin of these conformational preferences remains unclear. Although it is generally recognized that the gauche effect in carbohydrates is a solvent-dependent phenomenon, the mechanism through which solvent induces the gauche preference is not understood. In the present work, quantum mechanics and solvated molecular dynamics calculations were performed on two representative carbohydrates, methyl α-d-glucopyranoside and methyl α-d-galactopyranoside. We show that correct reproduction of the experimental rotamer distributions about the ω-angles is obtained only after explicit water is included in the molecular dynamics simulations. The primary role of the water appears to be to disrupt the hydrogen bonding within the carbohydrate, thereby allowing the rotamer populations to be determined by internal electronic and steric repulsions between the oxygen atoms. The results reported here provide a quantitative explanation of the conformational behavior of (1→6)-linked carbohydrates.

https://www.pnas.org/content/pnas/98/19/10541.full.pdf

Solvent interactions determine carbohydrate conformation

Biosynthesis of polyketides by trans-AT polyketide synthases

Odorant-binding proteins (OBPs) and chemosensory proteins (CSPs) are regarded as carriers of pheromones and odorants in insect chemoreception. These proteins are typically located in antennae, mouth organs and other chemosensory structures; however, members of both classes of proteins have been detected recently in other parts of the body and various functions have been proposed. The best studied of these non-sensory tasks is performed in pheromone glands, where OBPs and CSPs solubilise hydrophobic semiochemicals and assist their controlled release into the environment. In some cases the same proteins are expressed in antennae and pheromone glands, thus performing a dual role in receiving and broadcasting the same chemical message. Several reports have described OBPs and CSPs in reproductive organs. Some of these proteins are male specific and are transferred to females during mating. They likely carry semiochemicals with different proposed roles, from inhibiting other males from approaching mated females, to marking fertilized eggs, but further experimental evidence is still needed. Before being discovered in insects, the presence of binding proteins in pheromone glands and reproductive organs was widely reported in mammals, where vertebrate OBPs, structurally different from OBPs of insects and belonging to the lipocalin superfamily, are abundant in rodent urine, pig saliva and vaginal discharge of the hamster, as well as in the seminal fluid of rabbits. In at least four cases CSPs have been reported to promote development and regeneration: in embryo maturation in the honeybee, limb regeneration in the cockroach, ecdysis in larvae of fire ants and in promoting phase shift in locusts. Both OBPs and CSPs are also important in nutrition as solubilisers of lipids and other essential components of the diet. Particularly interesting is the affinity for carotenoids of CSPs abundantly secreted in the proboscis of moths and butterflies and the occurrence of the same (or very similar CSPs) in the eyes of the same insects. A role as a carrier of visual pigments for these proteins in insects parallels that of retinol-binding protein in vertebrates, a lipocalin structurally related to OBPs of vertebrates. Other functions of OBPs and CSPs include anti-inflammatory action in haematophagous insects, resistance to insecticides and eggshell formation. Such multiplicity of roles and the high success of both classes of proteins in being adapted to different situations is likely related to their stable scaffolding determining excellent stability to temperature, proteolysis and denaturing agents. The wide versatility of both OBPs and CSPs in nature has suggested several different uses for these proteins in biotechnological applications, from biosensors for odours to scavengers for pollutants and controlled releasers of chemicals in the environment.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/brv.12339

Beyond chemoreception: diverse tasks of soluble olfactory proteins in insects.

Regioselective de-O-benzylation with Lewis acids

1H NMR Analyses of Rotameric Distribution of C5-C6 bonds of D-Glucopyranoses in Solution

A simple method to determine the anomeric configuration of sialic acid and its derivatives by 13C-NMR

1H-NMR Studies on (6R)- and (6S)-deuterated (1–6)-linked disaccharides: assignment of the preferred rotamers about C5–C6 bond of (1–6)-disaccharides in solution

Up to 74 people die each year in Japan after being stung by Hymenopteran insects, with hornets (Vespa spp.) being among the worst offenders. Here we identify a volatile, multi-component alarm pheromone in the venom of the world's largest hornet, V. mandarinia, and use field bioassays to show that 2-pentanol is its principal active component, and that 3-methyl-1-butanol and 1-methylbutyl 3-methylbutanoate act synergistically with it. The compound 1-methylbutyl 3-methylbutanoate, which may also be a foraging-site-marking pheromone, elicits a strong defensive reaction in the sympatric prey hornet V. simillima xanthoptera. As these chemicals are sometimes used in food flavourings and as fragrances in cosmetics, it is possible that they might provoke a seemingly unwarranted hornet attack on humans.

Hiroshi Hori

Papers

Regioselective de-O-benzylation with Lewis acids

1H NMR Analyses of Rotameric Distribution of C5-C6 bonds of D-Glucopyranoses in Solution

A simple method to determine the anomeric configuration of sialic acid and its derivatives by 13C-NMR

1H-NMR Studies on (6R)- and (6S)-deuterated (1–6)-linked disaccharides: assignment of the preferred rotamers about C5–C6 bond of (1–6)-disaccharides in solution

Insect signalling: components of giant hornet alarm pheromone.