Lab

Laboratory of biomolecular interactions and transport

About the lab

The main research topic of the laboratory is focused on solving fundamental questions about mechanisms involved in a ligand transport through proteins, and implications of such processes for the function of the living cell. To obtain a more comprehensive picture, we also investigate the protein-ligands interactions at the functional sites as well as intra- and inter-protein interactions.

To make achieving these goals more effective, we develop new computational protocols and tools and apply them to the analysis of biomedically and biotechnologically relevant proteins.

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Featured research (6)

Haloalkane dehalogenase is an environmentally important biocatalyst that catalyzes the hydrolysis of the carbon-halogen bond. These are hydrolytic enzymes, requiring the presence of water molecules in their active site to perform their action. The active site of these enzymes is deeply buried, meaning that the substrate and water molecules have to travel to this location from the bulk solvent for reaction to occur. The transport pathways used by the waters and substrates are called tunnels. At present, molecular dynamics simulation is considered the best method to identify and characterize tunnels and capture the water transport across these tunnels. The preparation of the system and the water models used is a crucial part of how water transport through these transport pathways will be represented. First, we present our method to identify and evaluate water transport through these tunnels in massive simulation datasets. Next, we explore the effect of different popular water models on transport efficiency. The presented research provides new insights into the water transport in haloalkane dehalogenase through different permanent and transient tunnels. The methodology could be adopted by other researchers to systematically identify transport pathways used by water or other ligands in different enzymes with buried active sites. Finally, by comparing the result of such analyses with different water models, we provide an overview of the models used in the description of the transport process obtained.
Information regarding pathways through voids in biomolecules and their roles in ligand transport is critical to our understanding of the function of many biomolecules. Recently, the advent of high-throughput molecular dynamics simulations has enabled the study of these pathways, and of rare transport events. However, the scale and intricacy of the data produced requires dedicated tools in order to conduct analyses efficiently and without excessive demand on users. To fill this gap, we developed the TransportTools, which allows the investigation of pathways and their utilization across large, simulated datasets. TransportTools also facilitates the development of custom-made analyses. Availability and implementation TransportTools is implemented in Python3 and distributed as pip and conda packages. The source code is available at https://github.com/labbit-eu/transport_tools. Data are available in a repository and can be accessed via a link: https://doi.org/10.5281/zenodo.5642954. Supplementary information Supplementary data are available at Bioinformatics online.
Hydrolytic enzymes require the presence of water molecules in their active sites to perform their action. However, many enzymes have their active sites buried, which requires molecules of their cognate ligands and water to travel through transport pathways, called tunnels, to reach these sites. Since the tunnels relevant for water transport are often gated and only transiently opened molecular dynamics simulations are considered a method of choice for their study. Nonetheless, such investigation is hindered by the rare nature of tunnel opening and water transit. Here, we have intensively explored transient tunnels' conformations in three distinct hydrolytic enzymes with adaptive sampling simulations. These simulations revealed rare gating events comprising domain and loop movements, as well as several novel tunnels employed by water molecules that were not identified by traditional simulations so far. By mapping the flow of waters to the identified tunnel networks, we could link tunnels’ capacity to transport water with their properties. Additionally, we have evaluated our findings with various available water models to control for the dependency of our findings on the model used. The presented research will provide novel insights into mechanisms by which enzymes facilitate the utilization of water molecules during their catalytic action. Since many hydrolytic enzymes are biotechnologically and medically relevant, such knowledge can be beneficial for the engineering of enhanced biocatalysts or the development of new drugs. This research was supported by POWR.03.02.00­00­I006/17 project, National Science Centre, Poland (grant no. 2017/25/B/NZ1/01307), and grant of the Dean of faculty of biology, UAM (grant no. GDWB­05/2020). The computations were performed at the Poznan Supercomputing and Networking Center.
Information regarding pathways through voids in biomolecules and their roles in ligand transport is critical to our understanding of the function of many biomolecules. Recently, the advent of high-throughput molecular dynamics simulations has enabled the study of these pathways, and of rare transport events. However, the scale and intricacy of the data produced requires dedicated tools in order to conduct analyses efficiently and without excessive demand on users. To fill this gap, we developed the TransportTools, which allows the investigation of pathways and their utilization across large, simulated datasets. TransportTools also facilitates the development of custom-made analyses. TransportTools is implemented in Python3 and distributed as pip and conda packages. The source code is available at https://github.com/labbit-eu/transport_tools.
Progress in technology and algorithms throughout the past decade has transformed the field of protein design and engineering. Computational approaches have become well-engrained in the processes of tailoring proteins for various biotechnological applications. Many tools and methods are developed and upgraded each year to satisfy the increasing demands and challenges of protein engineering. To help protein engineers and bioinformaticians navigate this emerging wave of dedicated software, we have critically evaluated recent additions to the toolbox regarding their application for semi-rational and rational protein engineering. These newly developed tools identify and prioritize hotspots and analyze the effects of mutations for a variety of properties, comprising ligand binding, protein–protein and protein–nucleic acid interactions, and electrostatic potential. We also discuss notable progress to target elusive protein dynamics and associated properties like ligand-transport processes and allosteric communication. Finally, we discuss several challenges these tools face and provide our perspectives on the further development of readily applicable methods to guide protein engineering efforts.

Lab head

Jan Brezovsky
About Jan Brezovsky
  • Jan Brezovsky is a head of The laboratory of Biomolecular Interactions and Transport jointly at Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University in Poznan and the International Institute of Molecular and Cell Biology in Warsaw. The lab does research in Computational Biophysics and Bioinformatics. Their current project is Mechanisms of ligand transport in proteins.

Members (4)

Carlos Eduardo Sequeiros Borja
  • Adam Mickiewicz University
Bartłomiej Surpeta
  • Adam Mickiewicz University
Aravind Selvaram Thirunavukarasu
  • Adam Mickiewicz University
Dheeraj KUMAR Sarkar
  • Adam Mickiewicz University
Nishita Mandal
Nishita Mandal
  • Not confirmed yet