Projects 11711 and 11712 (GPU, LIN/WIN, Core21) to ADVANCED

[rafwiewiora]

Projects 11711 and 11712 have joined ADVANCED!

Stats:

11711:
# atoms: 31193 (mean over 11 RUNs, there is a slight variation)
credit: 14448
k-factor: 0.75
timeout: 7d
deadline: 10d

11712:
# atoms: 35094 (mean over 11 RUNs, there is a slight variation)
credit: 16571
k-factor: 0.75
timeout: 7d
deadline: 10d

Mixed precision is used (GPUs without DP are excluded).

In these projects, and already active on FAH 11707, 11708, 11709, and 11710 we are looking at histone lysine methyltransferase SETD8. This protein has been found overexpressed in a number of cancers including bladder cancer, non-small cell and small cell lung carcinoma, chronic myelogenous leukemia, hepatocellular carcinoma, and pancreatic cancer. In some cancers, it has been found to promote tumorigenesis, and it has been implicated in cancer invasiveness and metastasis [DOI: 10.1186/s13148-016-0268-4]. We are interested in understanding the conformational landscape of SETD8 in as much detail as possible, so that eventually selective small molecule inhibitors and chemical probes can be designed and tested. In these particular projects we’re looking at the histone methyltransferase SETD8 - in 3 different initial conformations - in all possible combinations with its co-factor SAM, by-product SAH, peptide substrate and methylated peptide product - we aim to explore conformations around all possible states of the catalytic cycle of this protein.