[In silico specificity determination of neoantigen-reactive T-lymphocytes].

Effective personalized immunotherapies of the future will need to capture not only the peculiarities of the patient's tumor but also of his immune response to it. In this study, using results of in vitro high-throughput specificity assays, and combining comparative models of pMHCs and TCRs using molecular docking, we have constructed all-atom models for the putative complexes of all their possible pairwise TCR-pMHC combinations. For the models obtained we have calculated a dataset of physics-based scores and have trained binary classifiers that perform better compared to their solely sequence-based counterparts.

Computer Modeling of N-Acetylglutamate Synthase: From Primary Structure to Elemental Stages of Catalysis.

Three-dimensional full-atom model of the enzyme complex with acetyl-CoA and substrate was constructed on the basis of the primary sequence of amino acid residues of N-acetyl glutamate synthase. Bioinformatics approaches of computer modeling were applied, including multiple sequence alignment, prediction of co-evolutionary contacts, and ab initio folding. On the basis of the results of calculations by classical molecular dynamics and combined quantum and molecular mechanics (QM/MM) methods, the structure of the active site and the reaction mechanism of N-acetylglutamate formation are described.

Structure of the Brain -Acetylaspartate Biosynthetic Enzyme NAT8L Revealed by Computer Modeling.

We report the results of computational modeling of a three-dimensional all-atom structure of the membrane-associated protein encoded by the gene, aspartate -acetyltransferase, which is essential for brain synthesis of -acetyl-l-aspartate (NAA). The lack of experimentally derived three-dimensional structures of NAT8L poses one of the obstacles in studies of the mechanism of NAA formation and understanding the precise role of NAA in neurological disorders. We apply a computational protocol employing the contact map prediction, folding, homology modeling, and refinement to obtain a structure of NAT8L with the aspartate and acetyl coenzyme A cofactors in the protein molecule.

[Variations of neuronal responses in cat cerebral cortex to somatic stimulation in the presence of additional stimulants].

Neuronal responses (areas 3, 4, 5) were registered in awake cats after electric stimulation of the contralateralis limb. External stimuli, food and defensive motivation inhibit short-latency neuronal reactions which were registered in control. When in the experiment there was electric stimulation of another limb instead of an external stimuli the neuronal reaction did not change.

[Inhibition of neuronal responses in the cat motor cortex, associated with attainment of a conditioned reflex when waiting for a flash of light].

Inhibition of neuronal spike reactions associated with reflex movements and induced by the light flare at different moments during the conditioned stimulation (1 s.) has been found in chronic experiments on cats. The light flare in the interval of maximum probability of the reflex realization has promoted a rise in the neuronal latency by 300-400 ms and a decrease of their duration almost twice.