Research topics

The Laboratory of Computational Biochemistry and Biophysics is devoted to the study of protein structure through bioinformatics- and structural biochemistry-based approaches. The in silicomethods mainly consist in molecular modeling, molecular docking and molecular dynamics of proteins with transport or enzymatic activity, or involved in signal transduction. 

Most of the current projects have their focus on modeling complex molecular assemblies, involving such diverse components as glycans and lipids in addition to one or more proteins. This is for instance the case of LCAT, a plasma protein involved in cholesterol metabolism, with the enzyme bound to apolipoprotein A-I and phospholipids in the form of discoidal HDL; of rabphilin3a and alpha-synuclein as interacting at neuronal synapses; of the Fc domain of an immunoglobulin and its alternative glycosylation patterns. The proteins are analyzed both in their canonical sequence and in the presence of mutations known to cause disease in humans, such as in LCAT deficiency or in Parkinson’s disease.

In parallel, with applications on toxicology rather than in pathology and pharmacology, a wide screening is being carried out on the interactions with protein targets by a number of substances with possible activity as endocrine disruptors or as teratogens.

From the outcome of the above research efforts, National, European and International Patents for protein activity modulators have been deposited by components of the laboratory.

 

Methods

Molecular modeling, to shape the 3D structure of proteins for which no experimental data are available
Molecular docking, to predict and asses both protein-protein and protein-ligand interactions
Molecular dynamics, to study the behavior of proteins and protein complexes in their biological milieu
In silico mutagenesis, to evaluate the impact of amino acid substitutions on structure and function
In silico high-throughput screening, to efficiently search for candidate ligands of carriers, channels, receptors, and enzymes, with medical or technical implications. 

 

Collaborations

Maria Pia Abbracchio, University of Milan, Italy
Albert Braeuning, German Federal Institute for Risk Assessment, Berlin (Germania)
Roberta Brambilla, The Miami Project To Cure Paralysis, Miami (USA)
Laura Calabresi, Centro Grossi Paoletti, University of Milan, Italy
Paolo Ciana, University of Milan, Italy
Raffaella Chiaramonte, University of Milan, Italy
Elena Chiricozzi, University of Milan, Italy
Alberto Corsini, University of Milan, Italy
Fabrizio Gardoni, University of Milan, Italy
Monica Di Luca, University of Milan, Italy
Stefania Iametti, University of Milan, Italy
Cesare Indiveri, University of Calabria, Cosenza, Italy
Marina Marinovich, University of Milan, Italy
Elena Menegola, University of Milan, Italy
Ingrid Miller, Institut für Medizinische Biochemie, Vienna (Austria)
Paola Minghetti, University of Milan, Italy
Francesco Molinari, University of Milan, Italy
Angelo Moretto, University of Milan, Italy
Andrea Pinto, University of Milan, Italy
Diego Romano, University of Milan, Italy
Mariafrancesca Scalise, University of Calabria, Cosenza, Italy
Maria Letizia Trincavelli, University of Pisa, Italy

 

Selected publications

Propiconazole is an activator of AHR and causes concentration additive effects with an established AHR ligand. Arch Toxicol. 2018 Dec;92(12):3471-3486. doi: 10.1007/s00204-018-2321-x. Epub 2018 Oct 6.

In silico description of LAT1 transport mechanism at an atomistic level. Front Chem. 2018 Aug 24;6:350. doi: 10.3389/fchem.2018.00350. eCollection 2018.

Role of the GM1 ganglioside oligosaccharide portion in the TrkA-dependent neurite sprouting in neuroblastoma cells. J Neurochem. 2017 Dec;143(6):645-659. doi: 10.1111/jnc.14146. Epub 2017 Sep 13.

A promiscuous recognition mechanism between GPR17 and SDF-1: Molecular insights. Cell Signal. 2016 Jun;28(6):631-42. doi: 10.1016/j.cellsig.2016.03.001. Epub 2016 Mar 10.

A computational approach to evaluate the androgenic affinity of iprodione, procymidone, vinclozolin and their metabolites. PLoS One. 2014 Aug 11;9(8):e104822. doi: 10.1371/journal.pone.0104822. eCollection 2014.