Title:	Understanding of enzymes catalysis
DNr:	SNIC 2020/5-250
Project Type:	SNIC Medium Compute
Principal Investigator:	Michal Biler <michal.biler@seznam.cz>
Affiliation:	Uppsala universitet
Duration:	2020-06-01 – 2021-06-01
Classification:	10407 10602 10603
Keywords:

Abstract

Within this project, we will study conformations, energetics and binding modes of enzymes in interaction with other ligands. Enzymes are essential biomolecules responsible for catalysis of many biological reactions. They accelerate chemical reactions, and convert substrate into a product. To study efficiency of such conversion, we model enzymes (in the wild-type form, and after introduction mutations), and we elucidate and compare enzyme (and corresponding mutants) reaction mechanisms of biological catalysis. One of the enzymes of our interest is Arylmalonate decarboxylase from Bordetella bronchiseptica (AMDase), which catalyzes breaking of C-C bond and stereoselective decarboxylation of aryl and alkenyl malonic acids. It converts pro-chiral substrates into chiral product in either (R) or (S)-form. Here, we will continue studying stereoselectivity of this enzyme and its mutant variants, and explain their distinct catalytic efficiency by means of electron valence bond (EVB) approach. We are also going to study other enzymes and their conformational changes with connection to catalytic rates. To have trustable results and reasonable statistics, we perform simulations of many replicas.