Dr. Verlinde studied pharmacy at the University of Leuven in Belgium when these studies were chemically oriented. As a graduate student he joined the lab of professor Camiel De Ranter at the same university. In 1988 he obtained his Ph.D. with as thesis K-opioids in the 6,7-benzomorphan series: x-ray crystallography, conformational analysis and pharmacophore modelling. In 1989 he joined the group of professor Wim Hol at the University of Groningen, The Netherlands, to gain expertise in protein crystallography and structure-based drug design. In 1992 he moved to the University of Washington as a post-doc, and in 1995 became a research assistant professor there and in 2000 associate professor of biochemistry. On July 31 2018 he retired from the university, and was honored with the title emeritus.

Research in the Verlinde group is in the field of structure-based drug design based on the Drug Design Cycle.

Our early work focused on the optimization of adenosine, an IC50 = 50 mM ligand, to design a potent inhibitor of trypanosomal glyceraldehyde-3-phosphate dehydrogenase with as structural input the complex of the enzyme with NAD. With the structure of the mammalian enzyme in hand we included selectivity as a design criterion. These efforts resulted in a 200 nM enzyme inhibitor that blocks trypanosomal glycolysis and growth in culture at low µM concentrations; no significant inhibition of the mammalian enzyme was seen. Subsequently, we explored the adenosine scaffold further in a focused library design study using the DOCK program. We examined two fusion positions on the scaffold, one with an amine library consisting of approximately 460 amines, and another position with a carboxylic acid library consisting of approximately 1400 acids. Of the virtual 644,000 compounds we selected 240 compounds for synthesis, resulting in 40 additional compounds that inhibit parasite growth in the low µ range.

We also designed a macrocyclic inhibitor of peptide deformylase using the FLO/QXP software. The idea behind the design was to reduce conformational freedom compared to a linear compound. The cyclic inhibitor showed potent inhibitory activity toward E. coli deformylase (Ki = 0.67 nM) and antibacterial activity against both Gram-positive and Gram-negative bacteria (MIC = 0.7-12 µg/mL).

In 2004 Dr. Fan and Dr. Verlinde collaborated to design a compound by linking two different ligands. It is a hetero-bivalent ligand of cholera toxin and serum amyloid-P component that promotes the dimerization of the two pentameric proteins.

Dr. Verlinde was also engaged within the framework of MMV (Medicines for Malaria Venture) in a collaboration with Drs. Van Voorhis, Buckner and Gelb. The goal was to design focused libraries of tetrahydroquinoline inhibitors of P.falciparum protein farnesyl-transferase to arrive at a new oral clinical candidate for malaria. In this project extensive use was made of the combinatorial library docking capabilities of the FLO/QXP software.

Dr. Verlinde, Dr. Buckner and Dr. Gelb are also using structure-based methods to design T.cruzi CYP51 inhibitors for treating patients with Chagas disease.

In the last couple of years Dr. Verlinde has been working with Drs. Fan, Buckner and Hol on the inhibition of trypanosomal methionyl-tRNA synthetases from various eukarotic parasites and bacteria. Subnanomolar inhibitors of trypanosomatid enzymes have been created that cure mice.

Since his retirement Dr Verlinde has been consulting for a pharmaceutical company with a focus in structure-guided development of antiviral compounds.