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| About Wilfried Langenaeker (Silicos) |
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Wilfried Langenaeker graduated as a licentiate in physical chemistry from the Free University of Brussels in 1989. In 1994, he obtained the title of Doctor in Sciences (Quantum Chemistry) with the greatest distinction. He was a postdoctoral Research Fellow of the Fund for Scientific Research from 1996 to 1999, affiliated to the Free University of Brussels. During this period his main focus was on Conceptual Density Functional theory, one of the reasons why he stayed at the University of North Carolina at Chapel Hill with Prof. Robert Parr, one of the authorities in conceptual quantum chemistry. This stay was financed by the means of a Fullbright award and a NATO research fellowship. In 1999, he joined the Janssen Research Foundation as a Senior Scientist in computational chemistry. In 2001 he received a “Standard of Leadership” award for his outstanding contribution to several discovery research projects at Johnson&Johnson Pharmaceutical R&D in Beerse (Belgium). In this period Wilfried also organized a series of lectures, given by prominent scientists such as Hugo Kubinyi and Johann Gasteiger, within J&J PRD, to introduce the medicinal chemists to different aspects of computational chemistry. Furthermore he was involved in the introduction of quantum chemistry as a functional tool in drug discovery at J&J PRD Beerse, not in the least through the introduction of the analytical technique of Vibrational Circular Dichroism (VCD). In 2003 Wilfried took the position of Senior Manager Post Approval Support at Janssen Pharmaceutica NV in Belgium. He held this position until 2005 when he co-founded Silicos NV, a spin-out of the Catholic University of Leuven, together with Hans De Winter, another employee of J&J PRD in Belgium. He currently holds the function of CEO at Silicos. Wilfried is (co-)author of more than 45 peer-reviewed scientific publications, one Chemical Review on Conceptual Density Functional theory and co-editor of three books.
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De novo and Fast-follower Design of Novel Therapeutic Compounds using the Cosmos™ Technology Platform
Wilfried Langenaeker, Silicos NV, Wetenschapspark 7, B-3590 Diepenbeek, Belgium
Cosmos™ is a proprietary genetic programming suite for the design of novel lead- and dru-like compounds. It is based on the combination of innovative virtual synthesis and optimization algorithms with commercially available as well as proprietary scoring algorithms, including Silicos’ proprietary Spectrophore™ technology, and commercial protein docking and ligand similarity software. Given this flexibility, Cosmos™ is speeding up the drug discovery process by generating novel compounds in a fast-follower strategy if a reference ligand is known, or by designing entirely new classes of compounds if information about the protein target structure is known. The heart of the Cosmos™ technology platform consists of a genetic programming suite linking proprietary virtual synthesis and optimization algorithms with commercial and proprietary software packages for the estimation of the quality of the generated molecules using scoring functions (Figure 1).
Examples of such scoring functions include the calculated binding affinity of the compound towards a protein active site, and the shape-based similarity of the compound to a particular reference ligand. Filtering on user-definable parameters with respect to lead- or drug-likeness and predicted ADME/Tox properties is directly incorporated in the design process. Experimental data, or other knowledge sources, can be incorporated in the procedure by means of user-defined weight factors.
The entire Cosmos™ procedure is based on a non-dominated sorting genetic algorithm (NDSGA) to introduce a multi-dimensional approach in the optimization step. This has the advantage that the molecules can be optimized for activity against a variety of protein targets at the same time, thereby paving the way to generate selectivity profiles and to introduce already in a very early stage information about possible side-effects (Figure 2).
The outcome of a typical Cosmos™ run are a set of molecules ranked by their scoring towards a user-defined target function. Synthetic accessibility is guaranteed by the implementation of experimentally derived rules that specify which fragments can be connected to each other.
This technology has been applied successfully in several cases. A demonstration of a fast follower approach as well as structure based de novo design using Cosmos™ will be given.
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