Due to their high intrinsic complexity, it is often difficult to understand how enzymes function and control the selectivity of numerous reactions. In spite of the fact that there has been an enormous progress in the field of experimental protein design and engineering, there are still many vital aspects that remain poorly understood. It is crucial to (a) develop computational protocols that can reliably describe and predict enzymatic function, (b) identify the mechanistic aspects and molecular determinants of the enzymatic process and (c) develop computational tools that can efficiently scan sequence space in the search for optimal biocatalysts.
From an organizational point of view, the workshop will be composed of four major sections:
1) Understanding Enzyme Mechanisms and Controlling Selectivity
"What I cannot create, I do not understand." Richard Feynman
A full understanding of the enzymatic mechanisms at the atomistic level is key for all rational design efforts. In addition, controlling selectivity is one of the most important issues in enzyme reengineering. While improving specific properties, enzymatic selectivity is often weakened. Selectivity control and computational insights of how to find effective and clever compromises between reactivity and selectivity will be discussed.
2) Design of New Enzymes
"Le monde de demain ne sera pas le fruit de nos réactions, il sera le fruit de nos créations." Jean-François Noubel
How can one tailor enzymes for non-natural functions? Is it possible to modify or completely redefine the function of an enzyme? Can we reprogram an existing scaffold for multiple enzymatic tasks?
3) Computational and Experimental Search and Optimization Procedures
"Somewhere, something incredible is waiting to be known." Carl Sagan
A wide range of methods have been reported to identify promising initial hits. In this section, we plan to discuss the construction of computational and experimental libraries and search algorithms that enable efficient exploration of chemical and sequence space.
4) Engineering Thermostability and Solvent Tolerance
"Qui veut faire de grandes choses doit penser profondément aux détails." Paul Valéry
One of the drawbacks of naturally occurring enzymes is their limited thermostability which restricts their use in industry. Engineering thermostability is a long-standing goal in protein design. In addition, optimizing enzymatic catalysts for different (non-aqueous) solvents can open additional design and process options.