1qch
From Proteopedia
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STRUCTURE, DYNAMICS AND HYDRATION OF THE NOGALAMYCIN-D(ATGCAT)2 COMPLEX DETERMINED BY NMR AND MOLECULAR DYNAMICS SIMULATIONS IN SOLUTION
Overview
The structure of the 1:1 nogalamycin:d(ATGCAT)2 complex has been, determined in solution from high-resolution NMR data and restrained, molecular dynamics (rMD) simulations using an explicit solvation model., The antibiotic intercalates at the 5'-TpG step with the nogalose lying, along the minor groove towards the centre of the duplex. Many drug-DNA, nuclear Overhauser enhancements (NOEs) in the minor groove are indicative, of hydrophobic interactions over the TGCA sequence. Steric occlusion, prevents a second nogalamycin molecule from binding at the, symmetry-related 5'-CpA site, leading to the conclusion that the observed, binding orientation in this complex is the preferred orientation free of, the complication of end-effects (drug molecules occupy terminal, intercalation sites in all X-ray structures) or steric interactions, between drug molecules (other NMR structures have two drug molecules bound, in close proximity), as previously suggested. Fluctuations in key, structural parameters such as rise, helical twist, slide, shift, buckle, and sugar pucker have been examined from an analysis of the final 500 ps, of a 1 ns rMD simulation, and reveal that many sequence-dependent, structural features previously identified by comparison of different X-ray, structures lie within the range of dynamic fluctuations observed in the MD, simulations. Water density calculations on MD simulation data reveal a, time-averaged pattern of hydration in both the major and minor groove, in, good agreement with the extensive hydration observed in two related X-ray, structures in which nogalamycin is bound at terminal 5'-TpG sites., However, the pattern of hydration determined from the sign and magnitude, of NOE and ROE cross-peaks to water identified in 2D NOESY and ROESY, experiments identifies only a few "bound" water molecules with long, residence times. These solvate the charged bicycloaminoglucose sugar ring, suggesting an important role for water molecules in mediating drug-DNA, electrostatic interactions within the major groove. The high density of, water molecules found in the minor groove in X-ray structures and MD, simulations is found to be associated with only weakly bound solvent in, solution.
About this Structure
1QCH is a Protein complex structure of sequences from [1] with NGM and NA as ligands. Full crystallographic information is available from OCA.
Reference
Structure, dynamics and hydration of the nogalamycin-d(ATGCAT)2Complex determined by NMR and molecular dynamics simulations in solution., Williams HE, Searle MS, J Mol Biol. 1999 Jul 16;290(3):699-716. PMID:10395824
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