Current projects

Current project

Revealing Molecular Mechanism of the Cyclic Dimeric Guanosine Monophosphate Hydrolysis

Bella Grigorenko, Marina Knyazeva, Ekaterina Kots, Alexander Nemukhin

Molecular modeling tools including the molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) approaches are applied to understand details of the enzyme hydrolysis of an important second messenger, the cyclic dimeric guanosine monophosphate (c-di-GMP). Phosphodiesterases containing the conserved eponymous Glu-Ala-Leu (EAL) motif asymmetrically cleave the c-di-GMP into the dinucleotide species 5′-pGpG (Figure EAL-1).

Revealing-molecular-mechanism
Figure EAL-1. A view on the EAL domain phosphodiesterase (left) and the chemical structure of the substrate (right).

Following simulation results we suggest a molecular model (Figure EAL-2) which can be used to clarify the mechanism of c-di-GMP hydrolysis.

Revealing-molecular-mechanism4

Figure EAL-2. A model of the active site.

 


Modeling molecular polymorphism of human enzymes

The project aims at understanding the role of point mutations of human proteins on the reaction mechanism of enzyme catalysis. Small GTPases, Aspartoacylase, Cholinesterases, Matrix Metalloproteinases, Carboxylesterase are the primary objects.


Mechanisms of enzymatic reactions of nucleoside triphosphate hydrolysis

The main focus of current research is on the hydrolysis reactions of guanosine triphosphate (GTP) by protein complexes Ras-GAP, Arl3-RP2.


Studies of enzymatic catalysis by metal-containing proteins

Zinc-containing (MMP) and magnesium-containing (PDE) proteins are on the top of the list.


Studies of enzymatic catalysis by cholinesterases

Different QM/MM and molecular dynamics methods are used to understand mechanisms of enzymatic catalysis by acetylcholinesterase and butyrylcholinesterase.


Molecular processes in photosensing proteins including GFP-type proteins and flavin-containing proteins  

Elementary reactions at the heart of photochemistry of proteins of the green fluorescent protein (GFP) family as well as of the flavin-containing domains are considered.


Molecular processes in the bacterial photosynthetic centers

Modeling structure and spectra of the light-harvesting complexes from photosynthetic centers