Posts by shilei

1) Message boards : Rosetta@home Science : protein-protein docking at Rosetta@Home (Message 78173) Posted 30 Apr 2015 by shilei Post: Dear Rosetta@home contributors, I am here to give some much overdue updates of "using sparse data to model protein-protein complexes". With the resources from Rosetta@home, I thoroughly tested several computational protocols to dock two proteins guided by sparse data from a benchmark set over 100 naturally occurring protein complexes. In the meantime, I participated partially in CAPRI experiments to blindly predict protein complexes. With two years of my research and many of your computational resources, we developed an improved workflow to use Rosetta for modeling protein complexes, such as the methodology for doing sampling, and criteria for model selection. I presented this work as a talk in the 54th Experimental Nuclear Magnetic Resonance Conference meeting in 2013. Unfortunately, we did not make enough breakthroughs to publish in a peer-reviewed journal. I learned that more sophisticated types of sampling algorithms to account for protein flexibility are needed to solve this problem. However, the new protocol turns out to be very useful in another more exciting applications. We currently use this as a tool to validate protein binder designs. Those designed protein binders have many practical applications. We are leveraging Rosetta global docking at R@H to validate in sillico protein designs. This method can improve protein design quality and speed up the design cycle. I am disappointed not be able to tackle this modeling project. But I am very glad that the protocol we developed are being used for protein engineering validations. I have moved on to work on protein design in industry since 2014. I sincerely appreciate your donation of computer resources to power Rosetta@Home during the time I have access to it. If you want to learn more about R@H, you can find more from Baker lab at University of Washington. I am sure my colleagues will be happy to tell you how much they have benefit from R@H. Best, Lei
2) Message boards : Number crunching : Minirosetta 3.50 (Message 76687) Posted 3 May 2014 by shilei Post: Hello, Sorry those are my boinc jobs that caused the computational errors on the clients. These are protein design calculations that aim to generate ideal protein topology to bind cancer target PD1. To generate a good structure, it requires searching a large space in both protein topology (composition and arrangement of protein secondary structures) and protein conformation. The generated structure undergoes strict filtering to ensure good quality control. This most of time results in few or no structures even after a couple of hours of computing. We used boinc to survey a large number of protein topologies on the order of 100,000 (each topology is sampled on the order of 10-100 times). The initial results can be used to guide further focused sampling on promising topologies. I am not sure what caused the malloc errors and quick terminating of the computations. Some of my jobs which are set up in the same way return good structures. I will work together with the boinc team to resolve this problem and prevent those from happening in the future. At last, I really appreciate your generosity to donating your computational resources. This speeds up a lot with our efforts to find binders that can potentially cure diseases. I have benefit a lot from boinc to design binders for Ebola virus very recently. Thanks for the feedback. Best regards, Lei
3) Message boards : Rosetta@home Science : protein-protein docking at Rosetta@Home (Message 75692) Posted 3 Jun 2013 by shilei Post: Dear Rosetta@home contributors, Here is an update on using sparse data to model protein-protein complexes. The ability to predict protein complexes structures has direct impact on computationally designing protein binders. There are several exciting disease-related protein design projects in the Rosetta community. Improvement in the computational methods can increase protein design quality and speed up the design cycle. Modeling protein complexe structure is equivalent to model two monomeric protein modeling protein and their docking to each other. Considering the challenges in modeling monomer protein structures (CASP), it is not surprising that this is a very difficult problem. In the past year, we have developed a new method to tackle this problem by using sparse experimental data and evolutionary information. Both approaches have been successfully applied to monomeric protein modeling (http://www.sciencemag.org/content/327/5968/1014.short and CASP10). We are combining this to model protein complexes. Inherent to this problem, we need large amount of computational resources to sample protein-complex conformational spaces. The resources from Rosetta@Home are invaluable and efficient for us to develop, test and apply our methods. I sincerely appreciate your donation of computer resources to power Rosetta@Home. I hope to update you soon when these results get published. Best, Lei
4) Message boards : Number crunching : Mini Rosetta Version 3.41. (Message 74267) Posted 13 Nov 2012 by shilei Post: Sincere apology for all the Zdock errors. The jobs failed due to one missing file in some of the zip files. I have downsized/withdrawn all the WUs. Sorry for the irresponsible submissions. Thanks for your contribution of WUs. It won't happen again.
5) Message boards : Rosetta@home Science : protein-protein docking at Rosetta@Home (Message 72147) Posted 15 Jan 2012 by shilei Post: Hi Rosetta@home, my name is Lei Shi, a postdoc in Baker's lab. My work is protein-protein docking with sparse experimental data. Many proteins carry their functions by interacting with other protein. Predicting protein interactions are thus important to understand their function. Computational prediction of protein complex structures using docking is an important approach toward this problem. The success and challenges of Rosetta docking have been highlighted by Chu's previous posts. Successful prediction of complex structures requires correctly capturing the protein-protein interactions at the interface and structures for each protein in their bounded form. This is still an unsolved problem due to the enormous number of degrees of freedom. Due to this reason, scientists are most of time solving the problems using tedious and costly experimental approaches, such as Xray or NMR etc. In my project, I will work to incorporate sparse experimental data into Rosetta docking. These experimental data is usually easily available in the early stages of experiment. Although sparse and ambiguous in nature, these limited data is very powerful guiding computational modeling. Combined with Rosetta methodology, this approach has proven to be very successful in protein structure prediction as highlighted in the science paper from the Baker's group in 2010 (NMR Structure Determination for Larger Proteins Using Backbone-Only Data, link at: http://www.sciencemag.org/content/327/5968/1014.short). My goal is to use similar information from experiments to improve the accuracy of protein complex structure using Rosetta dock. This will be useful to speed up the process of determine high-resolution complex structures with limited efforts in experiment investigation. Many previous Baker lab members, including Prof. Jeffrey Gray and Dr. Chu Wang etc, have laid the ground work. As a relatively new member (08/2011) to the Baker's lab, I am very excited for this project. Of course, the work will not be done with contributions and donations of your computational resources. Thank you all for your participation. Lei