Molecular Dynamics Simulations on Cyclin Dependent Kinases 2
and 5. Contribution to Designing New Inhibitors and
Understanding Mechanism of Activation/Inhibition

D 2007

Molecular Dynamics Simulations on Cyclin Dependent Kinases 2 and 5. Contribution to Designing New Inhibitors and Understanding Mechanism of Activation/Inhibition

BÁRTOVÁ, Iveta, Michal OTYEPKA, Zdeněk KŘÍŽ and Jaroslav KOČA

Basic information

Original name

Molecular Dynamics Simulations on Cyclin Dependent Kinases 2 and 5. Contribution to Designing New Inhibitors and Understanding Mechanism of Activation/Inhibition

Name in Czech

Molekulová dynamika na cyklin dependentních kinázách 2 a 5

Authors

BÁRTOVÁ, Iveta, Michal OTYEPKA, Zdeněk KŘÍŽ and Jaroslav KOČA

Edition

Praha, Modeling Interaction in Biomolecules III, p. 31--31, 1 pp. 2007

Publisher

MFF KU

Other information

Language

English

Type of outcome

Stať ve sborníku

Field of Study

10610 Biophysics

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

Organization unit

Faculty of Science

Keywords in English

molecular dynamics cyclin dependent kinase

Abstract

ORIG CZ

V originále

We will show in this paper how molecular dynamics simulations can provide important information even if they cover very short period of time (ns). Subject of the study will be CDK-2 and CDK-5 enzymes, members of the family of Cyclin-dependent kinases (CDKs) that control the progression of the cell cycle and participate in a subset of apoptosis programs [1]. The first part will be focused on solvation while the other one to the mechanism of activation/inhibition. The interactions between the protein and the solvent were analyzed and protein regions with a high density of water molecules as well as tightly bound water molecules were determined [2] by using MD simulations [3]. A number of water molecules that were in longer contact with the protein were identified and compared with X-ray crystallography data [4]. We will show in the lecture how tracing tightly bound water molecules can be used in drug design. MD simulations are also used to help explaining structural implications on mechanism of activation and inhibition by phosphorylation. Simulations on CDK-2 and CDK-5 are compared to assess the differences and similarities between the two kinases in terms of (i) roscovitine binding, (ii) regulatory subunit association, (iii) conformational changes in the T-loop following CDK/regulatory subunit complex formation, and (iv) specificity in CDK/regulatory subunit recognition [5].

In Czech

Molekulová dynamika na cyklin dependentních kinázách 2 a 5

Links

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

Citovat

BÁRTOVÁ, Iveta, Michal OTYEPKA, Zdeněk KŘÍŽ and Jaroslav KOČA. Molecular Dynamics Simulations on Cyclin Dependent Kinases 2 and 5. Contribution to Designing New Inhibitors and Understanding Mechanism of Activation/Inhibition. In Modeling Interaction in Biomolecules III. Praha: MFF KU, 2007, p. 31--31.

@inproceedings{755045,
   author = {Bártová, Iveta and Otyepka, Michal and Kříž, Zdeněk and Koča, Jaroslav},
   address = {Praha},
   booktitle = {Modeling Interaction in Biomolecules III},
   keywords = {molecular dynamics cyclin dependent kinase},
   language = {eng},
   location = {Praha},
   pages = {31--31},
   publisher = {MFF KU},
   title = {Molecular Dynamics Simulations on Cyclin Dependent Kinases 2 and 5. Contribution to Designing New Inhibitors and Understanding Mechanism of Activation/Inhibition},
   year = {2007}
}

TY  - JOUR
ID  - 755045
AU  - Bártová, Iveta - Otyepka, Michal - Kříž, Zdeněk - Koča, Jaroslav
PY  - 2007
TI  - Molecular Dynamics Simulations on Cyclin Dependent Kinases 2 and 5. Contribution to Designing New Inhibitors and Understanding Mechanism of Activation/Inhibition
PB  - MFF KU
CY  - Praha
KW  - molecular dynamics cyclin dependent kinase
N2  - We will show in this paper how molecular dynamics simulations can provide important information even if they cover very short period of time (ns). Subject of the study will be CDK-2 and CDK-5 enzymes, members of the family of Cyclin-dependent kinases (CDKs) that control the progression of the cell cycle and participate in a subset of apoptosis programs [1]. The first part will be focused on solvation while the other one to the mechanism of activation/inhibition. The interactions between the protein and the solvent were analyzed and protein regions with a high density of water molecules as well as tightly bound water molecules were determined [2] by using MD simulations [3]. A number of water molecules that were in longer contact with the protein were identified and compared with X-ray crystallography data [4]. We will show in the lecture how tracing tightly bound water molecules can be used in drug design. MD simulations are also used to help explaining structural implications on mechanism of activation and inhibition by phosphorylation. Simulations on CDK-2 and CDK-5 are compared to assess the differences and similarities between the two kinases in terms of (i) roscovitine binding, (ii) regulatory subunit association, (iii) conformational changes in the T-loop following CDK/regulatory subunit complex formation, and (iv) specificity in CDK/regulatory subunit recognition [5].
ER  -

BÁRTOVÁ, Iveta, Michal OTYEPKA, Zdeněk KŘÍŽ and Jaroslav KOČA. Molecular Dynamics Simulations on Cyclin Dependent Kinases 2 and 5. Contribution to Designing New Inhibitors and Understanding Mechanism of Activation/Inhibition. In \textit{Modeling Interaction in Biomolecules III}. Praha: MFF KU, 2007, p.~31--31.

Detailed Information on Publication Record