Računalniško načrtovanje terapevtskih proteinov

diplomsko delo visokošolskega strokovnega študijskega programa I. stopnje

Žan Smrekar (Author), Urban Bren (Mentor), Janez Konc (Co-mentor)

Abstract

Z uporabo računalniških programov in simulacij lahko predvidimo in predstavimo situacijo iz resničnega sveta oziroma se ji precej približamo. Kompleksnejše simulacije modelirajo potek interakcij, ki so ključne pri razumevanju delovanja in razvoju novih zdravilnih učinkovin. Pri zdravljenju rakavih bolezni postaja vse pomembnejša uporaba imunoterapije, kjer gre za pristop k zdravljenju raka z uporabo terapevtskih proteinov oziroma bioloških zdravil, ki izboljšajo in obnovijo človeški imunski sistem. Med biološka telesa spadajo tudi monoklonska protitelesa (rituksimab, pembrolizumab, obinutuzumab ...), ki lahko delujejo na različne načine. Pogosto se uporabljajo kot inhibitorji rakastih celic, agonisti ali signalne molekule. Protitelesa delujejo v zdravstvu popolnoma zadovoljivo, vendar obstajajo primeri, ko ne dosežejo želenega učinka in imajo negativne stranske učinke. Zaradi takšnih primerov se v uporabo vključujejo novi terapevtski proteini afimeri. V primerjavi s protitelesi gre za manjše proteine, ki se vežejo na tarčne molekule s podobno afiniteto in jih generirajo ter proizvajajo s procesi, za katere ne potrebujejo živih organizmov. V diplomski nalogi smo se osredotočili na protitelesa, ki tarčno delujejo na receptor CD20, izražen na površini limfocitov B. Naša naloga je bila računalniško načrtovati terapevtski protein afimer s podobno vezavo in afiniteto. Problema smo se lotili s pomočjo računalniških programov. Ustrezna monoklonska protitelesa smo poiskali z uporabo spletnega strežnika ProBiS. Za analizo in grafični pregled vezavnih mest smo uporabili računalniški program PyMol in za modeliranje končne konformacije afimera vključili vtičnik PyMod 2.0. V diplomskem delu je prikazano računalniško modeliranje afimera, ki se veže na epitop človeškega receptorja CD20 s podobno afiniteto, kot je vezava med receptorjem in protitelesi.

Keywords

imunoterapija;monoklonska protitelesa;afimer;receptor CD20;diplomske naloge;

Data

Language:	Slovenian
Year of publishing:	2019
Typology:	2.11 - Undergraduate Thesis
Organization:	UM FKKT - Faculty of Chemistry and Chemical Engineering
Publisher:	[Ž. Smrekar]
UDC:	004.94:616-097.3(043.2)
COBISS:	22674454
Views:	903
Downloads:	142
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	English
Secondary title:	Computational design of therapeutic proteins
Secondary abstract:	Computer programmes and simulations enable us to anticipate and present the real life situation or examine it closely. The more complex simulations model the course of interactions, which are crucial for understanding the operation and the development of new healing substances. Cancer treatment increasingly involves the use of immunotherapy – type of cancer treatment involving therapeutic protein and biological bodies respectively, which improve and restore the human immune system. The biological antibodies include monoclonal antibodies (rituximab, pembrolizumab, obinutuzumab,...), which can function in various ways. They are often used as cancer cell inhibitors, agonists or signaling molecules. Antibodies have proven to be functioning satisfactorily with some exceptions in which they fail to achieve the desired effect or even cause side effects. In order to prevent such situations, new therapeutic proteins called affimers are starting to be used. Compared to the antibodies, they are smaller proteins, which bind with target molecules having similar affinity and are generated and produced without the presence of living organisms. The thesis focuses on antibodies which target the CD20 receptor measured on the lymphocyte B surface. The task was to computationally design the therapeutic protein affimer with a similar binding and affinity. The research included computer programmes. The appropriate monoclonal antibodies were obtained via the internet browser ProBis. For the analysis and the graphical overview of binding sites the computer programme PyMol was used. The plug-in PyMod 2.0 was used for modelling of the final conformation of the affimer. The thesis describes the computational modelling of the affimer which binds with the epitope of the CD20 human receptor with a similar affinity as the binding of the receptor and antibodies.
Secondary keywords:	immunotherapy;monoclonal antibodies;affimer;CD20 receptor;PyMol;ProBiS;
Type (COBISS):	Bachelor thesis/paper
Thesis comment:	Univ. v Mariboru, Fak. za kemijo in kemijsko tehnologijo
Pages:	XIII, 62 str.
ID:	11214928