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The protein-protein interactions- molecular modelling study


Tomić, Sanja; Wade, Rebecca; Wang, Ting; Bertoša, Branimir; Gabdoulline, Razif
The protein-protein interactions- molecular modelling study // 6th Central European Symposium on Theoretical Chemistry - Book of Abstracts / Anne-Marie Kelterer (ur.).
Graz: TU-Graz, 2007. str. L12-L12 (predavanje, nije recenziran, sažetak, ostalo)


Naslov
The protein-protein interactions- molecular modelling study

Autori
Tomić, Sanja ; Wade, Rebecca ; Wang, Ting ; Bertoša, Branimir ; Gabdoulline, Razif

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
6th Central European Symposium on Theoretical Chemistry - Book of Abstracts / Anne-Marie Kelterer - Graz : TU-Graz, 2007, L12-L12

Skup
6th Central European Symposium on Theoretical Chemistry

Mjesto i datum
Litschau, Austrija, 22-27.09.2007

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
Protein-protein interactions; molecular modelling

Sažetak
The signal transduction and regulatory processes in cell are based on protein-protein interaction, and they are very sensitive to protein mutations. Herein I shall give an overview of our theoretical studies accomplished for two sets of protein complexes: Barnes- Barstar and complexes between Ras and its effectors, proteins Raf and RalGDS. Ras is a small guanosine triphosphate (GTP)-binding protein that serves as a switch in the mitogen-activating protein kinase pathway (MAPK). In its active, on conformation (GTP bound), Ras interacts with Raf, a Ser/Thr specific protein kinase, an immediate downstream target of Ras in MAPK. Another protein that Ras interacts with is Ral guanine nucleotide dissociation stimulator (RalGDS). This interaction is connected with the control of cytoskeletal rearrangements. Consequences of certain Ras mutations are uncontrolled growth and division of cells, and the mutated Ras proteins are frequently found in diverse human tumours. Barnase is the extracellular ribonuclease and Barstar is its intracellular inhibitor. This is one of the tightest known protein complexes with Kd of about 10-14M. We determined the dominating interactions in the above mentioned complexes (Fig. 1) and influence of the single point mutations on their stability, and derived the system specific QSAR (Quantitative Structure Activity Relationship) models for estimating binding free energy.1, 2 To find out what is the net electrostatic contribution to formation of these protein-complexes we accomplished Poisson-Boltzmann electrostatic calculations. The association rates of the designed mutants were calculated by using Brownian dynamics (BD) simulations.

Izvorni jezik
Engleski

Znanstvena područja
Kemija



POVEZANOST RADA


Projekt / tema
098-1191344-2860 - Proučavanje biomakromolekula računalnim metodama i razvoj novih algoritama (Sanja Tomić, )

Ustanove
Institut "Ruđer Bošković", Zagreb