Sequence and structure-based methods were used to characterize molecular determinants of mutational hotspots in protein kinases.
Biochemical and mutational characterisation has identified several determinants of NS2-3 cleavage [10-13] [10-13]
In this review, we discuss the potential genomic determinants of host anti-tumour immunity – mutational load, driver alterations, mutational processes and neoantigens – and their relationship with immunity in breast cancer.
In vitro studies established segments of amyloidogenic proteins and de novo designed peptides as suitable model systems to investigate sequence determinants of fibril formation (e.g. mutational effects) [49] [54].
DOI: http://dx.doi.org/10.7554/eLife.07864.005 After the second step of the mutational pathway from AncSR1 to AncSR1+RH, some of the derived determinants of specificity begin to appear, and the ancestral determinants are further weakened.
The latter finding is in apparent contradiction with mutational studies indicating that crucial diltiazem binding determinants overlap with determinants of PAA sensitivity located deeply in the channel pore (Hering et al., 1996; Kraus et al., 1998; Berjukow et al., 1999; Hockerman et al., 2000; Dilmac et al., 2003).
Important determinants of tumour behaviour are likely to be DNA mutational or rearrangement events, which produce oncogenes with dominant gain of function or tumour suppressor genes with recessive loss of function.
Mutational status of KRAS and EGFR, and EGFR copy number are potential determinants of cetuximab activity.
Instead, ancestral determinants of binding were weakened and derived determinants gradually strengthened as mutational combinations were assembled.
Similarly, response to mutations (using mutation-accumulation experiments [ 6]) identified TATA boxes and trans-mutational target sizes (number of proteins influencing the expression of a focal gene) as determinants of neutral variability.
