Marcel L. Verdonk

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The Chemscore function was implemented as a scoring function for the protein-ligand docking program GOLD, and its performance compared to the original Goldscore function and two consensus docking protocols, "Goldscore-CS" and "Chemscore-GS," in terms of docking accuracy, prediction of binding affinities, and speed. In the "Goldscore-CS" protocol, dockings(More)
A procedure for analyzing and classifying publicly available crystal structures has been developed. It has been used to identify high-resolution protein-ligand complexes that can be assessed by reconstructing the electron density for the ligand using the deposited structure factors. The complexes have been clustered according to the protein sequences, and(More)
We present a large test set of protein-ligand complexes for the purpose of validating algorithms that rely on the prediction of protein-ligand interactions. The set consists of 305 complexes with protonation states assigned by manual inspection. The following checks have been carried out to identify unsuitable entries in this set: (1) assessing the(More)
We present a novel atom-atom potential derived from a database of protein-ligand complexes. First, we clarify the similarities and differences between two statistical potentials described in the literature, PMF and Drugscore. We highlight shortcomings caused by an important factor unaccounted for in their reference states, and describe a new potential,(More)
This study addresses a number of topical issues around the use of protein-ligand docking in virtual screening. We show that, for the validation of such methods, it is key to use focused libraries (containing compounds with one-dimensional properties, similar to the actives), rather than "random" or "drug-like" libraries to test the actives against. We also(More)
We implemented a novel approach to score water mediation and displacement in the protein-ligand docking program GOLD. The method allows water molecules to switch on and off and to rotate around their three principal axes. A constant penalty, sigma(p), representing the loss of rigid-body entropy, is added for water molecules that are switched on, hence(More)
A major problem in structure-based virtual screening applications is the appropriate selection of a single or even multiple protein structures to be used in the virtual screening process. A priori it is unknown which protein structure(s) will perform best in a virtual screening experiment. We investigated the performance of ensemble docking, as a function(More)
The cytochromes P450 (P450s) are a family of heme-containing monooxygenase enzymes involved in a variety of functions, including the metabolism of endogenous and exogenous substances in the human body. During lead optimization, and in drug development, many potential drug candidates are rejected because of the affinity they display for drug-metabolising(More)
An empirical method for identifying interaction sites in proteins is described and validated. The method is based entirely on experimental information about non-bonded interactions occurring in small-molecule crystal structures. These data are used in the form of scatterplots that show the experimentally observed distribution of one functional group (the(More)
Although the crystal structure of the anti-cancer target protein kinase B (PKBbeta/Akt-2) has been useful in guiding inhibitor design, the closely related kinase PKA has generally been used as a structural mimic due to its facile crystallization with a range of ligands. The use of PKB-inhibitor crystallography would bring important benefits, including a(More)