The laboratory of molecular modeling and drug design develops algorithms and computer techniques and employs them, as well as other computational methods, for research in structural biology, modeling, and drug design.
A central activity in the laboratory is the development of novel optimization methods for solving the complex combinatorial problems that are an integral part of structural biology and drug design. A large scope of issues has already been addressed by our core technology, called “Iterative Stochastic Elimination” (ISE) which was used to search for optimal solutions to the construction of conformational ensembles, multiple loops in proteins, protein-ligand docking, protein design, cheminformatics and others.
The combinatorial optimization technology, Iterative Stochastic Elimination (ISE) was recently devised in our lab, and is now extended by PhD and MSc students to issues such as :
Modeling the conformations of large (>8 amino acids) loops and multiple loops
Studying the preexisting ensembles of protein loop conformations
Constructing conformational populations for computing properties of large ligands
Structure based design from molecular scaffolds and fragments
Predicting molecular properties from database comparisons
Assigning Drug likeness and molecular bioactivity to molecules
Ligand docking to proteins
Design of new functions in proteins
Designing protein sequences for inhibiting protein – protein interactions
Differentiating between folding and non-folding sequences
Constructing a new physical force field for proteins
A different development in our lab is a result of the application of sequence and structure alignments in protein kinases, which led to the finding of a new binding site in many kinases: a fatty acid, most probably myristoyl, binding pocket, which was previously shown to exist in c-Abl only. We have shown by several computational methods its existence in other kinases and its ability to bind fatty acid (myristoyl) derivatives.
Some of the MSc thesis in our lab are dealing with:
Designing inhibitors for the MBP of Abl
Designing inhibitors for the MBP in Src family kinases
Selectivity in the MBPs of kinases
Designing inhibitors for the substrate binding site in IGF1-R
Mechanism of differential aging of inhibited acetylcholinesterase
Chapters in Books
Goldblum, A., On the mechanisms of proteinases, In: Computational Approaches to Biochemical Reactivity (Naray-Szabo, G. and Warshel, A.,eds.), pp. 295-340.
Combinatorial Optimization Technology
Protein Kinase Inhibition
Molecular Bioactivity Indexes
Focused Molecular Libraries
Large Loop prediction