Cancer research experiments

Kinetic modulation of a disordered protein domain by phosphorylation

WU tags: KIDc22

Description

Experiment image

Not all proteins are naturally structured, and those that aren't are called intrinsically disordered proteins (IDPs). While they don't have structure, they do have many important roles in cell biology that are still being fully understood. They are often found mutated in many cancers at places that control the expression of genes and intra-cellular communication. In this work we show that a common chemical modification to IDPs known as phosphorylation can cause one IDP know as KID to change it's behavior. We further show that this could have important consequences for protein interactions, which affects all kinds of things like what genes are expressed and how signals are passed inside the cell.

Publications

  • N. Stanley. et al. Kinetic modulation of a disordered protein domain by phosphorylation. Nat. Commun. 5:5272 (2014)

BadgeRankNameCredit
wat1 Stoneageman432,230,350.00
wat2 RaymondFO*209,571,425.00
wat3 Firehawk195,325,675.00
wat4 flashawk169,940,000.00
wat5 Retvari Zoltan*168,413,875.00
wat6 Venec123,876,950.00
wat7 Rick A. Sponholz109,582,625.00
wat8 For the Universe ( Apaszko-Kaszkiety )103,799,025.00
wat9 Bedrich Hajek102,075,950.00
wat10 werdwerdus93,249,525.00
Number of contributors: 2838

Computational modeling of an EGFR single-mutation resistance to cetuximab in colorectal cancer treatment

WU tags: EGFR

Description

Experiment image

Extracellular S468R mutation of the epidermal growth factor receptor (EGFR) was recently identified as the cause of resistance to cetuximab, a widely used drug in colorectal cancer treatment. Here, we have determined the binding free energies of cetuximab's Fab V(H)-V(L) domains and endogenous EGF ligand to wild type and S468R EGFR by high-throughput molecular dynamics. This work provides a possible mechanism of resistance in terms of increased competition, an hypothesis that can be further validated experimentally.

Publications

  • I. Buch, N. Ferruz and G. De Fabritiis, Computational modeling of an EGFR single-mutation resistance to cetuximab in colorectal cancer treatment, J. Chem. Inf. Model., 2013, 53 (12), pp 3123–3126

BadgeRankNameCredit
wat1 Stoneageman77,231,380.00
wat2 Retvari Zoltan*76,352,566.00
wat3 comfortw64,158,341.00
wat4 Venec47,340,586.00
wat5 Bikermatt34,035,023.00
wat6 escape31,904,255.00
wat7 mclaver31,857,293.00
wat8 ftpd27,038,309.00
wat9 netwraith24,550,849.00
wat10 WirelessDude23,912,620.00
Number of contributors: 3349

Molecular simulations of the SH2 and ligand peptide binding affinity

WU tags: pYEEI, SH2

Description

The SH2 is a protein domain involved in protein-protein interactions. This particular domain plays a major role in cell communication on the sigalling processes for cell growth and development. However, the end goal for running such simulations is not to expand the knowldege on this particular system, but to use it as a model for developing methods to calculate protein-protein binding affinities.
Such methods will be very useful, for example, in the study of why certain wrong forms of proteins stop interacting with other partner proteins, as a way to give explanation to phenoma observed in diseases such as Cancer

Publications

  • I. Buch, S. K. Sadiq and G. De Fabritiis, Optimized potential of mean force calculations of standard binding free energy, J. Chem. Theory Comput., 7, 1765–1772 (2011)
  • I. Buch, M. J. Harvey, T. Giorgino, D. P. Anderson and G. De Fabritiis, High-throughput all-atom molecular dynamics simulations using distributed computing, J. Chem. Inf. and Mod. 50, 397 (2010)

BadgeRankNameCredit
wat1 Merlyn [The Scottish Boinc Team]17,681,701.00
wat2 STE\/E [BlackOpsTeam]17,134,517.00
wat3 UL111,109,988.00
wat4 Reset@Alice10,038,828.00
wat5 Bigred9,774,517.00
wat6 [C@B] jesusnt9,235,067.00
wat7 yamashin8,772,004.00
wat8 [AF>HFR>RR] Jim PROFIT8,476,835.00
wat9 Carat@precure8,378,504.00
wat10 Localizer8,319,548.00
Number of contributors: 2932