ИСТИНА

Voltage-gated potassium channel Kv10.2 is expressed in the nervous system and its mutants are involved in development of epileptic encephalopathy and autistic features (Yang et al., 2013), tumor emergence and development (Camacho, 2006). Knowledge of the three-dimensional channel structure and details of its organization is an important step to understanding the mechanisms of its functioning and determining possible experimental techniques. Goal of the current study was an improvement of previously built Kv10.2 channel spatial structures (Ju, 2006; Sokolova, 2012) using homology modeling method and molecular dynamics simulation. There are several templates available to the moment including eag domain-CNBHD complex of the mouse EAG1 channel (pdb-code 4LLO), full-length Shaker potassium channel Kv1.2 (pdb-code 3LUT), C-linker/CNBHD of zELK channels (pdb-code 3UKT) and others. But there are still no templates for many fragments that led to necessity of partial de novo modeling. Molecular dynamic simulation was performed using processing package Gromacs with all-atom force field opls-AA. Analysis of molecular trajectory allowed estimating dynamical characteristics of channel, supposing interdomain interactions, and predicting positions of important mutations. Results of the conducted investigation have a great interest at both the academic and the industrial levels.