Emiliano Brini presents his work on using MELD to predict protein structures and interactions.
Our new paper "Molecular modeling of biomolecules by paramagnetic NMR and computational hybrid methods" is now available from BBA Proteins and Proteomics.
This is intended as an easy to digest review of paramagnetic NMR methods and associated computational modelling strategies.
I'm extremely proud to announce that the MacCallum lab was awarded a five year grant from CIHR for our project aimed at developing new molecular diagnostics for crystal arthropathies. This is an exciting project with great results to date, and we're grateful for funding to push it further.
Overall success rates in this year's CIHR Project Grant were only 16 percent, which is completely unhealthy and reflects funding that has been flat for 15 years. Success rates outside of BC and Ontario were half the national average. Such regional disparities will not lead to the thriving research environment that Canadians need.
While I'm fortunate to have obtained a grant in the in the current climate, I hope that the Minister of Science recognizes the need for improved funding for science in Canada.
Professor Aatto Laaksonen visited and gave a CMS seminar on methods for hierarchical coarse graining.
It was truly a pleasure to welcome my postdoctoral advisor, Dr. Ken Dill, to visit us in Calgary. Ken's seminar focused on how physical chemistry influences and limits the behaviour of cells. As expected, it was thought provoking, with great engagement from the audience.
I recently attended the Molecular Sciences Software Institute (MOLSSI) workshop hosted at Stanford. MOLSSI is an NSF-funded consortium that aims to advance molecular simulation software, infrastructure, education, standards, and best practices. The workshop focused on the topics of conformational sampling, molecular simulation workflows, and emerging applications of machine learning in molecular science. The discussion was great and it was a wonderful opportunity to engage with people I hadn't met before, as well as old friends.
Two postdocs in the lab were recently awarded fellowships.
Congratulations to Kala, who received an AIHS postdoctoral award, and Maggie, who received an NSERC PDF!
Recent results in the field of protein folding have showed that atomistic molecular dynamics (MD) simulations can correctly fold small proteins, providing insights on their structures as well as on their folding pathways. Those simulations, however, remain computationally expensive. MD simulations are deterministic: once the initial positions and velocities have been set, the trajectory for the protein under study is derived by numerically solving Newton's second law with tiny time steps, hence the long simulation times. If additional information (such as "forming a hydrophobic core") could be added to steer the simulations, it is expected that they could be sped up significantly. However, proper inclusion of such additional information requires caution as it needs to satisfy the thermodynamic principles of Boltzmann's law. The authors have developed a proper statistical mechanics framework for this purpose, they have applied this framework to successfully fold twenty small proteins, including ubiquitin, a millisecond folder. Inclusion of this framework into folding simulations using MD is shown to yield up to five orders of magnitude faster computational folding times than traditional MD.
Our latest work on the development of a grid-based correction to the backbone dihedral angles in the Amber forcefield has be published in the Journal of Chemical Theory and Computation.
In this paper, we derive a grid-based correction for use with the Amber ff12SB force field in combination with the GBNeck and GBNeck2 implicit solvation models. This correction improves the relative balance of random coil, alpha helix, and beta sheet secondary structures.