Computational analysis of a kinase superfamily

Postgraduate Thesis uoadl:2820851 343 Read counter

Unit:
Κατεύθυνση Βιοπληροφορική
Library of the School of Science
Deposit date:
2018-11-30
Year:
2018
Author:
Merantzi Vasia
Supervisors info:
Καθηγητής Κ. Βοργιάς, Τμήμα Βιολογίας ΕΚΠΑ
Original Title:
Υπολογιστική ανάλυση οικογένειας κινασών
Languages:
Greek
Translated title:
Computational analysis of a kinase superfamily
Summary:
Calcium (Ca2+) is one of the most widespread and important second messengers. It acts as a second message in a variety of cellular responses by regulating downstream signaling pathways and by participating in a variety of important biological processes. Calmodulin (CaM), which acts as the primary intracellular calcium receptor in almost all eukaryotic cells, forms calcium (Ca2+ -CaM) complexes and thus controls the activity of more than 120 different enzymes and proteins. One of the most important target proteins of calmodulin is the family of Calcium-Calmodulin Dependent Kinases (CAMKs). The kinase-calmodulin interaction leads to critical conformational changes in the kinase molecule, which are necessary for the physiological functions of the kinase. Ca2 + -CaM-kinase complexes regulate different cellular functions, including regulation of gene expression, cell death (apoptosis), cytoskeleton reorganization, learning, memory and many others.
Interactions of the calmonutin-dependent kinases and the calmodulin play a key role both in clarifying the mechanisms of cell responses such as changes in calcium concentration. However, the available structural data concerning the mechanisms governing the interactions between the calmodulin-dependent kinases and the calmodulin are incomplete, as only two cases of experimentally determined complexes were determined. Todate, structural information has been obtained mainly from complexes of calmondulin with small kinase peptides. Additionally, while the interaction has high specificity, no conserved sequences of the target proteins has been recorded.
Based on the above, the aim of this diploma thesis was the computational study of the interactions of the calmodulin-dependent kinases with the calmodulin by computational methods exploiting the co-evolutionary information.
The computational coexpression protocol applied in the study of interactions between the calmodulin-dependent kinases and the calmodulin contributed both to the finding of possible coexpression sites between the two protein groups and to the functional commenting of key amino acid residues interactions. In particular, the information resulting from the coevolution methods during the study of the above complexes was confirmed both by the experimentally determined complexes and by means of directed anchoring methods. Finally, this stydy highlighted protein parts that are actively involved in conformational modifications during the interaction of the molecules.
The results of this diploma thesis on the one hand reinforce the view that the use of co-evolutionary information is an important tool for exploring and commenting on the functions of protein families. On the other hand, the co-evolution data related to calmodulin and calmodulin-dependent kinases enrich the study of the mechanism and the nature of the interactions between them, a research field that targets the design and development of drugs for a variety of pathological conditions, diseases of the nervous system or different forms of cancer.
Main subject category:
Science
Keywords:
kinases, co-evolution, bioinformatics, calmodulin
Index:
Yes
Number of index pages:
2
Contains images:
Yes
Number of references:
133
Number of pages:
178
Merantzi_Master_thesis.pdf (7 MB) Open in new window