Specific effects of the coupling of protein reactions to slow protein structure dynamics are studied. We focus on accumulation of structural changes produced in consecutive protein cycles and eventually modifying the cycle itself. We showed previously [Christophorov et al., Chem. Phys. 256, 45 (2000); Goushcha et al., Biophys. J. 79, 1273 (2000)] that such an effective interaction between cycles can cause the thresholdlike emergence of a new stable functional state of the protein macromolecule. To elucidate this mechanism, we have performed numerical modeling of the reaction kinetics in a two-state system coupled to diffusion in the corresponding conformational potentials. Specifically, the model is related to the charge separation and recombination processes in photosynthetic reaction centers (RCs). It is shown that the percentage of RCs remaining structurally deformed after recombination, until the next photoexcitation event (“memory-bearing” centers), can be quite low. Nonetheless, under prolonged photoexcitation it is sufficient for driving eventually all the RCs to a state of high charge-separation efficiency. The dependence of this efficiency on quasistationary photoexcitation intensity is pronouncedly hysteretic. The conformation potentials anharmonicity extends the bistability range noticeably, thereby improving RC adaptation properties. Experimental protocols to detect the memory-bearing centers in the RC ensemble are proposed, simulated and tested, disqualifying the electron escape to hypothetical redox traps. The technique proposed can be used in the studies of cooperative effects under repeated cycling of biomolecules.

The general theory of the single-file multiparticle diffusion in the narrow pores could be greatly simplified in the case of inverted bell-like shape of the single-particle energy profile, which is often observed in biological ion channels. There is a narrow and deep groove in the energy landscape of multiple interacting ions in such profiles, which corresponds to the pre-defined optimal conduction pathway in the configurational space. If such groove exists, the motion of multiple ions can be reduced to the motion of single quasiparticle, called the superion, which moves in one-dimensional effective potential. The concept of the superions dramatically reduces the computational complexity of the problem and provides very clear physical interpretation of conduction phenomena in the narrow pores.

No abstract

We aimed to determine the value of the paired-pulse inhibition (PPI) in the auditory cortex in patients with Parkinson's disease (PD) and analyze its dependence on clinical characteristics of the patients. The central (Cz) auditory evoked potentials were recorded in 58 patients with PD and 22 age-matched healthy subjects. PPI of the N1/P2 component was significantly (P < .001) reduced for interstimulus intervals 500, 700, and 900 ms in patients with PD compared to control subjects. The value of PPI correlated negatively with the age of the PD patients (P < .05), age of disease onset (P < .05), body bradykinesia score (P < .01), and positively with the Mini Mental State Examination (MMSE) cognitive score (P < .01). Negative correlation between value of PPI and the age of the healthy subjects (P < .05) was also observed. Thus, results show that cortical inhibitory processes are deficient in PD patients and that the brain's ability to carry out the postexcitatory inhibition is age-dependent.