A new paper using ACEMD has been published in JACS under the title Thumbs Down for HIV: Domain Level Rearrangements Do Occur in the NNRTI-Bound HIV-1 Reverse Transcriptase stemming from a collaboration between University College London (UK) and Universitat Pompeu Fabra (Spain) researchers.
In this work researchers unveiled previously undescribed closed conformations in drug-bound HIV-1 RT which suggesting that “allosteric modulation is effected via the alteration of the kinetic landscape of conformational transitions upon drug-binding”. In the publication researchers also state that “a more detailed understanding of the mechanism of NNRTI inhibition and the effect of binding upon domain motion could aid the design of more effective inhibitors and help identify novel allosteric sites.”
The work was performed through an ensemble molecular dynamics strategy using ACEMD and aggregate simulation time of ~0.6 µs.
D. W. Wright, S. K. Sadiq, G. De Fabritiis, P. V. Coveney, Thumbs Down for HIV: Domain Level Rearrangements Do Occur in the NNRTI-Bound HIV-1 Reverse Transcriptase, J. Am. Chem. Soc., 2012, 134 (31), 12885–12888. http://pubs.acs.org/doi/abs/10.1021/ja301565k
alejandroNew paper in JACS on conformational characterization of HIV-1 RT
A Science paper titled “Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions” by the group of Professor R. C. Stevens at The Scripps Research Institute in La Jolla, CA (USA) has confirmed the role of sodium ions in the allosteric regulation of GPCRs as it had been modeled by Selent et al. in 2010 using high-throughput MD simulations on ACEMD.
Results by Stevens Group shed on the importance of endogenous small molecules at specific binding sites as control mechanisms of membrane proteins. Such concept exceeds the common view of allostery via pharmacological ligands. The results have profound effects on the current understanding of the functional mechanisms of GPCRs, a broad family of proteins that comprises many of today’s pharmacological targets.
In that regard, computational modeling of small molecule-protein interactions using ACEMD has proven powerful tool to predict unknown solvent-derived effects on protein function.
– Liu W., et al., Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions, Science 2012: 337 (6091), 232-236. DOI:10.1126/science.1219218
– Selent J., et al., Induced Effects of Sodium Ions on Dopaminergic G-Protein Coupled Receptors, PLOS Computational Biology 2010, 6, e1000884. DOI:10.1371/journal.pcbi.1000884
We are pleased to inform that Acellera Ltd has now a business development point of contact in North America. Ignasi Buch, a PhD in Computational Biophysics and an experienced user of ACEMD, is based in Pittsburgh, PA (USA). He can be contacted by USA, Canada and Mexico customers for questions regarding any of Acelera’s expanding line high-throughput molecular dynamics based products, as well as for the development of strategic partnerships.
Current computational tools allow performing microsecond long simulations routinely at low cost. In a perspective article Harvey and De Fabritiis discuss in the context of drug discovery the potential of performing molecular dynamics simulations in high-throughput (HT-MD) and argue the time for HT-MD is here. http://dx.doi.org/10.1016/j.drudis.2012.03.017
Sattelle et al. use ACEMD to produce microsecond simulations of pyranose ring puckering and study its dependence on anomeric configuration. These results appear in the Journal of Physical Chemistry B: http://pubs.acs.org/doi/pdfplus/10.1021/jp303183y http://pubs.acs.org/doi/pdfplus/10.1021/jp303183y