“Structural Bioinformatics: Sequence/Structure/Function Relationship Studies of Proteins”

Business Building 903, Beirut campus

The Department of Computer Science and Mathematics is hosting a seminar titled “Structural Bioinformatics: Sequence/Structure/Function Relationship Studies of Proteins” to be given by Dr. Joseph Rebehmed, expert in Computational Chemistry from the IMPMC Laboratory, Université Pierre et Marie Curie (Paris–France).

The lecture will be available in Nicol 222 on the Beirut campus and Science 608 on the Byblos campus.

Abstract: Structural bioinformatics is the branch of bioinformatics that studies the three-dimensional (3D) structure and function of biological macromolecules such as proteins. Proteins are complex macromolecules that play many critical roles for almost all biological and cellular activities in living organisms. They are made of a sequence of small units, called amino acids, that determines each protein’s 3D structure and its specific function(s). Experimental procedures for studying proteins are inherently low throughput and expensive making computational approaches a growing research area. These in silico approaches are essential components to address theoretical and experimental questions of modern biological research. Research in the area of protein structural bioinformatics deals with the elucidation of the 3D structures of proteins, the discovery of principles of protein folding and architecture, evolution and the sequence/structure/function relationships. It also allows identifying and characterizing biological behaviors such as binding sites, not only to understand molecular interactions in natural and disease states, but also to exploit information on protein structures for the design of compounds with application in the pharmaceutical and biotechnological industries.

To illustrate the various applications and interests in this field, I will present some of my recent research works. First, I will show my work on Baeyer-Villiger monooxygenase (BVMO) enzymes that catalyze the transformation of linear and cyclic ketones into their corresponding esters and lactones by introducing an oxygen atom into a C-C bond. This bio-reaction has numerous advantages compared to its chemical version. We searched for new potential BVMOs in the databases using sequence homology. We performed multiple sequence alignments to categorize true BVMOs and to study the conservation of structurally and/or functionally important amino acids during evolution. We succeeded to update the signature pattern to easily identify this family of enzyme. BVMOs require two cofactors which are crucial for catalysis. Amino acids at the vicinity of the FAD and NADPH cofactors were found to be highly conserved during the evolution and the details of the interactions were emphasized. We used a supercomputer to predict the 3D structures of the new BVMOs and to perform molecular dynamics simulations on them. All the data will be grouped in a database that we are currently building and that will be freely available for the scientific community. This work allowed experimentalist collaborators to improve the BVMO activities. Secondly, I will present my work on post-translational modifications (PTM) in proteins. PTMs play important roles in modulating various biological functions, but are often forgotten. We have therefore built PTM-SD: a database of structurally resolved and annotated. PTM-SD gives valuable information on observed PTMs in protein 3D structure, which is of great interest for studying sequence–structure–function relationships at the light of PTMs, and could provide insights for comparative modeling and PTM predictions protocols. PTM-SD can be freely accessed at

Finally, I will show my work on GPCR proteins that are the targets of one-third to one-half of all marketed drugs. We predicted the best 3D structure of the CXCR4 GPCR protein and the orientation and position of the CVX15 ligand in the protein binding site during the international GPCR Dock 2010 assessment. Our predicted complex was the closest to the experimental result.

All are welcome to attend.