Orodja za inovativno oblikovanje zdravil / Tools for innovative drug design

Ta projekt je v ospredju trenutnih
raziskovalnih trendov na področju molekularnega modeliranja. Razvili bomo nove
metode molekularnega modeliranja, ki temeljijo na teoriji kemijskih grafov,
veji matematične kemije, ki se ukvarja z diskretnimi strukturami v kemiji.Poseben poudarek bo na razvoju novih
algoritmov za predvidevanje mest vezave proteinov (ProBiS) in novih spletnih
orodij za modeliranje farmacevtsko zanimivih molekul – ProBiS Tools (algoritem,
baza podatkov, spletni strežnik).
Orodja ProBiS bodo prva, ki bodo omogočala
identifikacijo interakcij med beljakovinskimi strukturami, napovedovanje
selektivnosti in vezave liganda ter spremljanje učinkov ohranjenih voda in
različic zaporedja na vezavo liganda, da preseže človekovo vpletenost v
oblikovanje zdravil.

Naš cilj je razviti prostodostopen spletni
atlas interakcij z beljakovinami za napovedovanje genskih variacij, povezanih z
interakcijami z zdravili in razvojem bolezni – ProBiS-ATLAS vseh razpoložljivih
mest vezave na beljakovine v PDB s preslikanimi ligandi in različicami
zaporedja. Atlas bo vključeval tudi informacije o učinkih različic zaporedja na
vezavo za vsak specifični ligand v PDB. Ta novo razviti pristop bo še posebej
koristen v okviru natančne medicine.

Naša orodja ProBiS bodo omogočila kombiniranje več sicer nepovezanih področij raziskovanja. Kljub velikemu
potencialu za konkretno uporabo naših rezultatov v določenih tehnoloških in
industrijskih sektorjih je glavni poudarek naših raziskav še vedno na razvoju
splošnih, novih matematičnih metod in algoritmov na področju molekularnega
modeliranja in tako prispeva k svetovni zakladnici znanja.

V projektu sodelujejo številni raziskovalci z
odličnimi znastvenimi rezultati, ki trenutno delajo v Sloveniji in zagotavljajo
raziskave na najvišji možni ravni.
This project is at the forefront of current
research trends in the field of molecular modeling. We will develop new
molecular modeling methods based on chemical graph theory, a branch of
mathematical chemistry dealing with discrete structures in chemistry.

A special focus will be on the development of
new algorithms for the prediction of protein binding sites (ProBiS) and new web
tools for modeling of pharmaceutically interesting molecules – ProBiS Tools
(algorithm, database, web server).

The ProBiS Tools will be the first to allow
the identification of interactions between protein structures, the prediction
of ligand selectivity and binding, and the monitoring of the effects of
conserved waters and sequence variants on ligand binding, to surpass human
involvement in drug design.

We aim to develop a free web-based protein
interaction atlas to predict genetic variations involved in drug interactions
and disease development – ProBiS-ATLAS of all available protein binding sites
in the PDB with mapped ligands and sequence variants. The atlas will also
include information on the effects of sequence variants on binding for each
specific ligand in the PDB. This newly developed approach will be particularly
useful in the context of precision medicine.

Our ProBiS Tools will make it possible to
combine several otherwise unrelated fields of research, i.e. graph theoretical
approaches, genome sequence studies, protein structures and molecular dynamics
simulation.

Despite the great potential for the concrete
application of our results in specific technological and industrial sectors,
the main focus of our research is still on the development of general, new
mathematical methods and algorithms in the field of molecular modeling, and
thus represents a contribution to the overall scientific knowledge.

The project involves a number of researchers with
excellent publishing records, currently working in Slovenia guaranteeing
research at the highest possible level.