Funkce proteinu v multidomenovych proteinech je casto nesena jednou funkcni domenou na pozadi komplexni proteinove struktury. Vyznam ostatnich domen je casto nejasny protoze mohou ovlivnovat chovani funkcni domeny nekolika zpusoby. Bud omezuji ci moduluji funkci primo sterickym mezidomenovym usporadanim na principu protein-protein interakce nebo neprimo, za pomoci alostericke modulace kde princip teto kontroly je nesen charakterem sousednich domen ovlivnujici dynamiku a specificitu funkcni domeny. Cilem prace je pomoci simulacnich metod v soucinosti s experimentem objasnit principy alostericke modulace v nove navrzenych modelovych dvoudomenovych proteinech a vysvetlit do jake miry je struktura domeny spousedici s funkcni domenou a jeji dynamika urcujicim faktorem chovani dvoudomenoveho fuzniho proteinu. Prace predpoklada zakladni znalosti vypocetnich metod molekularniho modelovani, fyzikalne - chemickych principu smerujicich k vypoctum volne energie systemu, statistickych metod a dovednosti v oboru skriptovacich funkci v prostredi Linux a zakladnich metod bioinformatiky. Jde o projekti na pomezi teorie-experiment, kdy experimentalni metody slouzi k overeni a testovani navrzenych mechanismu, pripadne definuji skalu pouzitelnych vypocetnich postupu. Prace je primarne teoreticka.
Předběžná náplň práce v anglickém jazyce
The function of a protein in multi-domain proteins is often carried by a single functional domain against the background of a complex protein structure. The significance of other domains is often unclear because they can affect the behavior of functional domains in several ways. Either restrict or modulate the function by a steric inter-domain arrangement on the principle of protein-protein interaction or indirectly, by means of allosteric modulation where the principle of this control is carried by the nature of adjacent domains affecting the dynamics and specificity of the functional domain. The aim of the work is to use simulation methods in conjunction with the experiment to elucidate the principles of allosteric modulation in newly proposed model two-domain proteins and to explain to what extent the structure of the domain adjacent to the functional domain and its dynamics determine the behavior of two-domain fusion proteins. The work presupposes basic knowledge of computational methods of molecular modeling, physical - chemical principles leading to the calculation of free energy of the system, statistical methods, skills in the field of scripting functions in the Linux environment and basic methods of bioinformatics. It is a project on the border of theory-experiment, where experimental methods are used to verify and test the proposed mechanisms, or define the range of applicable computational procedures. The work is primarily theoretical.
- zadáno vedoucím/školitelem