Výpočetní chemie - Jaroslav Koča
Masarykova univerzita Masarykova univerzita
Výpočetní chemie - Jaroslav Koča

PhD Témata

1. Engineering the glycans of stem cells to have required bioactivity – a computational study combined with an experiment

Supervisor: prof. RNDr. Jaroslav Koča, DrSc.
Consultants: Ing. Igor Tvaroška, DrSc.


Investigations throughout the end of the 20th century revealed that cell migration is coordinated by chemoattractants present within endothelial beds. The cell migration is encoded by a series of overlapping steps, and tissue-specific migration is controlled by a discrete combination of various receptors present on circulating cells. The first step of the cascade, tethering contact of cells on the endothelium, is governed by interactions of selectins (E-, P-, and L-selectin) with their ligands. Selectin ligands are specialized carbohydrate determinants, consisting of sialofucosylations containing an alpha(2,3)-linked sialic acid substitutions and an alpha(1,3)-linked fucose modification displayed as the tetrasaccharide sialyl Lewis X (sLex) that are exhibited on the glycoform CD44. However, in some human mesenchymal stem cells, the terminal alpha(2,3)-sialyllactosamine moieties are lacking alpha(1,3)-fucosylation at N-acetylglucosamine to have the complete sLex determinant and, therefore, are lacking E-selectin ligand. The enzyme responsible for the alpha(1,3)-fucosylation is fucosyltransferase VI (FucTVI). The Ph.D. study will attempt to shed some light on the role of alpha(1,3)-fucosylation on a function of selectin ligands.

Keywords: chemoattractants, alpha(1,3)-fucosylation, ligands selection, glycans

2. Partial atomic charges – a clue to predict chemical and biological behaviour of biomacromolecules

Supervisor: prof. RNDr. Jaroslav Koča, DrSc..


Nowadays, large amount of structural data about biomacromolecules is available and the number of resolved structures is growing rapidly. This information provides us a great opportunity to analyse the data and to reach a key biological information. Partial atomic charges belong to very promising molecular characteristics. They describe the distribution of electron density in a molecule, and, therefore, they provide clues regarding the chemical and biological behaviour of molecules. Thanks to advanced computational approaches, they can became available also for large and extra-large biomacromolecules. As they belong to biomacromolecular chemical characteristics, they can consequently be very helpful in revealing biological implications. For example, they can serve for a prediction of point mutations effect, for understanding allostery and other biomacromolecular activation mechanisms, sometimes processes that are very difficult to access by experimental approaches.
The thesis will focus on two challenges. First is development a methodology to calculate atomic charges in biomacromolecular systems in a reasonable time and with a reasonable accuracy, and second is application of atomic charges on revealing selected biological problems where such biomacromolecules are involved.

Keywords: biomacromolecules, partial atomic charges, data analysis

3. Characterizing sequence-structure-function relationships: A multi-dimensional approach for evaluating similarity in structural biology data

Supervisor: prof. RNDr. Jaroslav Koča, DrSc.
Consultants: Mgr. Ing. Crina-Maria Ionescu, Ph.D.


Understanding the similarity between the sequence and/or structure of biomolecules has been key to inferring evolutionary relationships and predicting the function of biomolecules. We propose a novel approach for defining and evaluating the similarity between biomolecules. The approach is based on representing structural biology data as a square matrix of biomolecular structure elements and their properties; we then define similarity as the result of comparing the eigenvalues and eigenvector spaces determined for the biomolecules compared. Such a test of statistical similarity is intended to determine whether the compared biomolecules share features of structure, function, biological pathway, or affinity for a certain range of binding partners.

Keywords: biomolecules, sequence-structure-function relationship, data analysis