Most standard molecular docking algorithms take into account only ligand flexibility, while numerous studies demonstrate that receptor flexibility may be also important. While some efficient methods have been proposed to take into account local flexibility of protein side chains, the influence of large-scale domain motions on the docking results still represents a challenge for computational methods. In this work we compared the results of ATP docking to different models of Ca-ATPase: crystallographic apo- and holo-forms of the enzyme as well as "flexible" target models generated via molecular dynamics (MD) simulations in water.
View Article and Find Full Text PDFATP is an important substrate of numerous biochemical reactions in living cells. Molecular recognition of this ligand by proteins is very important for understanding enzymatic mechanisms. Considerable insight into the problem may be gained via molecular docking simulations.
View Article and Find Full Text PDFCopper transport by the P(1)-ATPase ATP7B, or Wilson disease protein (WNDP),1 is essential for human metabolism. Perturbation of WNDP function causes intracellular copper accumulation and severe pathology, known as Wilson disease (WD). Several WD mutations are clustered within the WNDP nucleotide-binding domain (N-domain), where they are predicted to disrupt ATP binding.
View Article and Find Full Text PDFPhosphorylation of histidine-containing proteins is a key step in the mechanism of many phosphate transfer enzymes (kinases, phosphatases) and is the first stage in a wide variety of signal transduction cascades in bacteria, yeast, higher plants, and mammals. Studies of structural and dynamical aspects of such enzymes in the phosphorylated intermediate states are important for understanding the intimate molecular mechanisms of their functioning. Such information may be obtained via molecular dynamics and/or docking simulations, but in this case appropriate force field parameters for phosphohistidine should be explicitly defined.
View Article and Find Full Text PDFWNDP (Wilson's disease protein) is a copper-transporting ATPase that plays an essential role in human physiology. Mutations in WNDP result in copper accumulation in tissues and cause a severe hepato-neurological disorder known as Wilson's disease. Several mutations were surmised to affect the nucleotide binding and hydrolysis by WNDP; however, how the nucleotides bind to normal and mutated WNDP remains unknown.
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