Computational study of the dimethylphosphate hydrolysis as the reference system for the understanding of the restriction endonucleases mechanism

STŘELCOVÁ, Zora, Jakub ŠTĚPÁN, Petr KULHÁNEK, Paolo CARLONI and Jaroslav KOČA. Computational study of the dimethylphosphate hydrolysis as the reference system for the understanding of the restriction endonucleases mechanism. In IX Discussions in Structural Molecular Biology, Nové Hrady. 2011.

Basic information

• Original name: Computational study of the dimethylphosphate hydrolysis as the reference system for the understanding of the restriction endonucleases mechanism
• Authors: STŘELCOVÁ, Zora (203 Czech Republic, guarantor, belonging to the institution), Jakub ŠTĚPÁN (203 Czech Republic, belonging to the institution), Petr KULHÁNEK (203 Czech Republic, belonging to the institution), Paolo CARLONI (380 Italy) and Jaroslav KOČA (203 Czech Republic, belonging to the institution).
• Edition: IX Discussions in Structural Molecular Biology, Nové Hrady, 2011.

Other information

• Original language: English
• Type of outcome: Conference abstract
• Field of Study: 10403 Physical chemistry
• Country of publisher: Czech Republic
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• RIV identification code: RIV/00216224:14740/11:00050025
• Organization unit: Central European Institute of Technology
• Keywords (in Czech): enzymatická katalýza MutH ab-inito dynamika CPMD dimethyl fosfát metadynamika PMF lib
• Keywords in English: enzyme catalyses MutH ab-inito dynamics CPMD dimethylphosphate metadynamics PMF lib
• Tags: rivok

Abstract

Understanding enzymatic mechanisms is essential knowledge for further medicine and biotechnology development. Our long-standing effort is aimed at the explanation of the reaction mechanism of endonucleases (enzymes cleaving DNA chain(s)) using computational approaches. According to the published experimental and theoretical results, the suggested mechanism is SN2 hydrolysis of the phosphate backbone. [1] Presented work is focused on the study of simplified model of the enzymatic reaction. This model consists of dimethylphosphate and the nucleophile (water, hydroxyl ion) attacking the phosphodiester bond. The hydrolysis was simulated using Car Parrinello Molecular Dynamics (CPMD) [2] in vacuum and in water. The reaction free energy profiles were evaluated using metadynamics [3] and obtained results were compared to the experimental data [4]. The model serves as a reference system for the upcoming simulation of the enzymatic reactions.

Links

• GD301/09/H004, research and development project: Name: Molekulární a strukturní biologie vybraných cytostatik. Od mechanistických studií k chemoterapii rakoviny

Investor: Czech Science Foundation

• LC06030, research and development project: Name: Biomolekulární centrum

Investor: Ministry of Education, Youth and Sports of the CR, Biomolecular centre

• MSM0021622413, plan (intention): Name: Proteiny v metabolismu a při interakci organismů s prostředím

Investor: Ministry of Education, Youth and Sports of the CR, Proteins in metabolism and interaction of organisms with the environment

• 205872, interní kód MU: Name: Program developing interdisciplinary research POtential for the STudies of BIOMolecular INteractions (Acronym: POSTBIOMIN)

Investor: European Union, Program developing interdisciplinary research POtential for the STudies of BIOMolecular INteractions, Capacities