In silico methods are useful for predicting 3D structure of binding sites when experimental information is lack. The complex interaction between γ-crystallins and small ligands is a key element in understanding the lens transparency. In spite of the high sequence similarity of γ-crystallins, different numbers of pockets were automatically identified on their molecular surfaces. γC-crystallin ha...

Tony Ferrar*, Delphine Chamousset*, Veerle De Wever, Mhairi Nimick, Jens Andersen, Laura Trinkle-Mulcahy and Greg B. G. Moorhead Department of Biological Sciences, University of Calgary, 2500 University Dr, Calgary, Alberta, T2N 1N4, Canada Department of Cellular & Molecular Biology and Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON, Canada Department of Biochemistry & Mo...

Designing new and better chemotherapeutic compounds requires an understanding of the mechanism by which the drugs exert their biological eeects. This involves consideration of the geometry of the active site, determination of the geometry of the drug, and analysis of the t between them. This problem of drug-substrate t, often called the docking problem, can be greatly innuenced by uncertainty i...

Computational tools are essential in the drug design process, especially in order to take advantage of the increasing numbers of solved X-ray and NMR protein-ligand structures. Nowadays, molecular docking methods are routinely used for prediction of protein-ligand interactions and to aid in selecting potent molecules as a part of virtual screening of large databases. The improvements and advanc...

The docking complex is a molecular complex necessary for assembly of outer dynein arms (ODAs) on the axonemal doublet microtubules (DMTs) in cilia and flagella. The docking complex is hypothesized to be a 24-nm molecular ruler because ODAs align along the DMTs with 24-nm periodicity. In this study, we rigorously tested this hypothesis using structural and genetic methods. We found that the ODAs...

β-Secretase (BACE-1) constitutes an important target for search of anti-Alzheimer's drugs. The first inhibitors of this enzyme were peptidic compounds with high molecular weight and low bioavailability. Therefore, the search for new efficient non-peptidic inhibitors has been undertaken by many scientific groups. We started our work from the development of in silico methodology for the design of...

The use of QM/MM based methods to optimize and rescore GOLD derived cross-docked protein-ligand poses has been investigated using a range of fragment-like kinase inhibitors where experimental data have been reported. Particular emphasis has been placed on rationalizing the potential benefits of the method in the increasingly popular fragment based drug discovery area. The results of this cross-...

Screening for potential ligands and docking them into the binding sites of proteins is one of the main tasks in computer-aided drug design. Despite the progress in computational power, it remains infeasible to model all the factors involved in molecular recognition, especially when screening databases of more than 100,000 compounds. While ligand flexibility is considered in most approaches, the...

Nomenclature ∆F0 = Bow wave disturbance force ∆pdr = Drogue position offsets from equilibrium position ∆pdr/pr = Position error between drogue and probe ∆pdr/pr (T ) = Terminal position error ∆Rdr/pr = Radial error between hose and drogue FT = Tanker joint frame Fr, Fhd = Disturbance forces on receiver and hose-drogue Fbow = Disturbance force from bow wave effect pdr (t), ppr (t) = Current posi...

Structure-based virtual screens were carried out against beta-secretase (BACE1) to investigate the impact of ligand protonation on screening efficacy. A comparative evaluation of the performance and its dependence on ligand protonation states docking by Surflex, eHiTS, GOLD, and FlexX-Pharm was performed. Virtual screening performed by FlexX-Pharm (EF(1%)=69) and Surflex (EF(1%)=58) provided th...