Charge centers and formation of the protein folding core

Electrostatic interactions are important for protein folding. At low resolution, the electrostatic field of the whole molecule can be described in terms of charge center(s). To study electrostatic effects, the centers of positive and negative charge were calculated for 20 small proteins of known structure, for which hydrogen exchange cores had been determined experimentally. Two observations seem to be important. First, in all 20 proteins studied 30-100% of the residues forming hydrogen exchange core(s) were clustered around the charge centers. Moreover, in each protein more than half of the core sequences are located near the centers of charge. Second, the general architecture of all-alpha proteins from the set seems to be stabilized by interactions of residues surrounding the charge centers. In most of the alpha-beta proteins, either or both of the centers are located near a pair of consecutive strands, and this is even more characteristic for alpha/Beta and all-beta structures. Consecutive strands are very probable sites of early folding events. These two points lead to the conclusion that charge centers, defined solely from the structure of the folded protein may indicate the location of a protein's hydrogen exchange/folding core. In addition, almost all the proteins contain well-conserved continuous hydrophobic sequences of three or more residues located in the vicinity of the charge centers. These hydrophobic sequences may be primary nucleation sites for protein folding. The results suggest the following scheme for the order of events in folding: local hydrophobic nucleation, electrostatic collapse of the core, global hydrophobic collapse, and slow annealing to the native state. This analysis emphasizes the importance of treating electrostatics during protein-folding simulations.     

A grafting approach to obtain site-specific metal-binding properties of EF-hand proteins

The EF-hand calcium-binding loop III from calmodulin was inserted with glycine linkers into the scaffold protein CD2.D1 at three locations to study site-specific calcium binding properties of EF-hand motifs. After insertion, the host protein retains its native structure and forms a 1:1 metal-protein complex for calcium and its analog, lanthanum. Tyrosine-sensitized Tb3+ energy transfer exhibits metal binding and La3+ and Ca2+ compete for the metal binding site. The grafted EF-loop III in different environments has similar La3+ binding affinities, suggesting that it is largely solvated and functions independently from the host protein.     

Descriptive statistics of disallowed regions and various protein secondary structures in the context of studying twisted β-hairpins

A detailed analysis of polypeptide-chain backbone conformations was carried out for polypeptide-chain segments adjacent to β-turn regions, including the sites of disallowed conformations. A cross comparison of conformations was performed for disallowed regions of the Ramachandran plot and main types of β-turns and adjacent secondary structures. Based on the results, disallowed region 2 (II, II') in the Ramachandran plot was shown to coincide mainly with β-hairpins and, more exactly, twisted β-hairpins. The frequency of residues with angles ?_i, ψ_i that fall in region 2 (II, II') in the latter is 140 times higher than in common β-hairpins.     

Correlations of convulsive and hypoxic resistance in rats at different stages of ontogenesis

Hypoxic and convulsive resistances were studied in 3, 7, 14, 21, 40-day-old rats and in adults. Susceptibility to hypoxia was determined in pressure chamber by "lifting" the animals to the altitude of 12,000 metres. Convulsions were caused by intraabdominal injections of corazol. A correlation between hypoxic and convulsive resistances was found from 3 day after the birth. Their indexes were maximum at this period. Similar decrease of hypoxic and convulsive resistances was observed with the growth of the animals. Moreover the reduction in hypoxic resistance was more dramatic and reached its minimum on the 40th day. In grown up animals, resistance to hypoxia was higher, than in 40-day-old rats. Minimum latency period for development of status epilepticus was detected in 21-day-old rats.     

Corazol kindling in rats with different tolerance to hypoxia]

Research was conducted studying the peculiarities of development of pharmacological kindling in rats with different tolerance to hypoxia. Kindling was evoked by injecting subconvulsive doses of corazol (25 mg per kg) every day. Intensity of convulsions was expressed in points. Reliable distinction in intensity of convulsion between low-tolerant rats and high-tolerant rats to hypoxia was found on the 17th day of stimulation; amongst the group of low-tolerant rats the intensity of convulsions was found to be 2.46 + 0.30 points, and amongst the group of high-tolerant rats--1.20 + 0.22 points (p 0.05). On the 23rd day of injection the preparation convulsions in the group of low-tolerant rats reached up to 4.00 + 0.20 points and in the group of high-tolerant rats 2.28 + 0.45 points (p 0.01). The changes of violation of behavior were found to be different. Thus, the higher the individual resistance to hypoxia, the more is the resistance of the animal to the effect of epileptogens.     

Predetermined Conformations in Bends of Polypeptide Chains: A Geometric Analysis

Biophysics - β-Bends are typical local structures of the polypeptide chain, are widespread in proteins, and play an important structural and functional role. It is possible to expect a priori...     

The seasonal characteristics of the circadian rhythm of hypoxic resistance and convulsive resistance]

Hypoxic and convulsive resistances have daily rhythms, the pattern of which depends on the year season. Latent period of occurrence of epileptic seizures and time of life at the "height" of 11,000 m above the sea level undergo similar changes in autumn and spring. In winter minimal similarity between daily dynamics of each of these resistances and analogous ones in other seasons is observed, but rhythms of tolerance to hypoxia are maximally synchronized with the rhythms of convulsive resistance. In autumn hypoxic and convulsive resistances are minimal. Maximums of these indices are observed in different seasons: for tolerance to hypoxia it is summer, for convulsive resistance--spring.     

Stochastic electron acceleration in plasma waves driven by a high-power subpicosecond laser pulse

The mechanism of stochastic electron acceleration and heating by a picosecond laser pulse in underdense plasma is studied using particle-in-cell simulations and theoretical models. The formation of wide electron energy spectra in the simultaneously acting laser and plasma fields is analyzed. It is shown that electron scattering by turbulent plasma fluctuations excited through stimulated forward Raman scattering plays a governing role in the formation of high-energy tails in the electron distribution function.     

Effect of adaptation to hypoxia on the resistance of rats to the epileptogenic action of penicillin

The influence of adaptation to moderate hypoxia on anticonvulsive resistance of low tolerant rats has been investigated. Focal epilepsy was induced by penicillin application to sensorimotor cortex of the rat brain. Adaptation to hypoxia has been shown to increase the resistance of rats to epileptogenic penicillin effect which is manifested in the prolongation of the latent period of epileptiform discharges and less frequent epileptic fits. The mechanisms of the resistance increase remains to be investigated.     

Prospects of Non-drug Approaches to Alzheimer's Disease

Despite the urgency of the problem of prevention and treatment of neurodegenerative processes underlying Alzheimer's disease (AD) and other severe disorders of the central nervous system, therapeutic and prophylactic potential of drugs is yet insufficient. Numerous adverse effects of the drugs, which might improve cognitive function in patients with AD substantiate serious consideration of measures enhancing adaptive potential and mobilizing self-defense of the body. It is clear now that endogenous defense systems of the brain can limit progression of AD long after the onset of the disease. The measures mobilizing the self-defense include administration of natural adaptogens and various types of adaptation, such as adaptation to dietary restrictions, promotion of physical and mental activity, and adaptation to hypoxia. This review presents data supporting a hypothesis that non-drug activation of self-defense of the body can prevent cognitive decline induced by neurodegenerative processes in the brain by targeting key points of AD pathogenesis.