Structural Bioinformatics & Biocomputing

Main Focus

"In silico structural biology correlated with experiment"

Mission Statement

The Department of Bioinformatics & Structural Biochemistry (DBSB) was set in 1999 aiming to consistently implement computational biology techniques - bioinformatics, modeling, simulation - and use them to guide experimental research in molecular biology and biochemistry.

Overview

Historically the main focus of DBSB was the investigation of glycoprotein (GP) folding & degradation and the relation between glycosylation and GP structure. On this line DBSB works in co-ordination with the Department of Molecular Cell Biology and colleagues from the Department of Biochemistry, University of Oxford, UK. Results have shed light onto the structure of glycans attached to the nascent protein chain and their role in the ER quality control and degradation [1,7-5,14,20,33]. The way glycosylation affects GP structure was also assessed using bioinformatics approach. To this end DBSB has developed SAGS: "Structural Assessment of Glycosylation Sites" - a comprehensive Data Base curating structural information on glycans and glycoproteins, with significant applications in modeling biological systems at molecular level [4,13,15,20-21,32].

DBSB was also involved in more general aspects of the physics of protein folding and structure. Configurations along the folding pathway and in the native state are degenerate and the experimental data has to be interpreted in the frame of statistical mechanics. In collaboration with colleagues from CEA Saclay and Heidelberg University we have investigated unfolded and native protein states using molecular simulation in combination with Small Angle and Quasielastic Neutron Scattering.

These studies have resulted in a better understanding of the folding process and the motility gradients in proteins explaining their stability and ability to interact with other molecules [2,3,8-12].

Combining bioinformatics with principles of protein folding and dynamics results in many applications in molecular life sciences such as building probabilistic models when the experimental structures are not available, or probing in silico biomolecular interactions.

Presently a significant part of our work is devoted to developing techniques in this field and applying them to a variety of problems in structural biology and molecular medicine. For example in collaboration with colleagues from IBAR and Oxford University we continue to investigate the structural aspects of processes along the secretory pathway; with colleagues from Yale School of Medicine USA; Levin Cancer Institute USA; Warsaw University Poland we are looking into protein-DNA interactions in a number of systems relevant in molecular medicine & biotechnology[29,34,36,38,42,43]; with groups from Universities of California - Berkeley and Davis, Wageningen, Haifa, Zurich, MPI-Koln, INRA-France etc we are involved in investigating the molecular basis of plant-pathogen interaction [16-17,22-24,26-27,31,39,41,45-47].

The models generated so far in this process allowed us to make predictions upon systems behavior. Subsequently predictions were successfully validated experimentally and resulted in a better understanding of the molecular bases underlying the investigated biological functions - some of them with potentially important applications in molecular medicine, biotechnology and pharmacology [16-52].

Along the years, DBSB work was financed by a large number of national and international grants among of which we mention 1 EU-IP-FP6 ("Bioexploit": 2005-2011); 1 EU-FP5 ("Nonema": 2001-2004); 2 UK - Wellcome Trust ( "Tyrosinase Folding": 1998-2001; "Glycoprotein Database": 2002-2005) or the national grant PN-II-ID-PCE 168 ("in silico": 2007-2011); PN2-ID-PCE-2011-3-0342 "Modeling molecular complexes and assemblies with experimental and bioinformatic constraints" (2011-2016); L.Spiridon - PN-III-P1-1.1.-TE-2016-1852 "Free energy prediction of biomolecular processes using high speed robotic algorithms" (2018-2020); PN-III-P4-ID-PCE-2020-2444 "Usage of high speed robotic algorithms for in-silico assisted experimental research of large biomolecular systems" (2021-2023), and many other national research consortiums.

DBBS was also member of the MC of COST Action "Sustain" FA1208-11941: "Pathogen-informed strategies for sustainable broad-spectrum crop resistance" (2013-2018) while  AJ-P was also Co-PI in the USA-NIH grant 4R37 AI032524 "Structure of RAG1-RAG2-DNA complexes" (2012-2017) and NIH 1R01 AI137079-01A1/2018 "Function and evolutionary origin of RAG1 endonuclease" carried by Professor David Schatz from the Departmentof of Immunobiology, Yale School of Medicine.

Currently our group is involved in carying out two major FEDR funded consortium projects of national interest: ROGEN - Developing Genomic Research in Romania (2024 - 2029) and CANTAVAC - Development of Translational Research for Vaccines, Serums and other Biological Medicines (2024 - 2029) as well as in the EU Horizon Project COMBINE HLTH-2024-DISEASE-08