Amino Acids Thesis
For example, the commonly used PAM and BLOSUM matrices [1, 2] have been built based on the frequencies of amino acid substitutions observed in aligned protein sequences.
This measure, routinely used in programs such as BLAST , represents both evolutionary and functional similarity between amino acids.
The Rags are unusual GTPases in that they function as obligate heterodimers, which consist of Rag A or B bound to Rag C or D.
The Rag GTPases interact with m TORC1 and signal amino acid sufficiency by promoting the translocation of m TORC1 to the lysosomal surface, its site of activation.
Our specific interest is in peptide binding to proteins involved in antigen processing and presentation, such as the TAP transporter [4, 5] and MHC molecules.
In recent large-scale benchmark studies, the best performing prediction method for peptide: MHC class I binding is the Net MHC artificial neural network, outperforming linear methods such as SMM [6, 7].
Like BLOSUM62, this matrix captures well-known physicochemical properties of amino acid residues.SLC38A9 forms a supercomplex with Ragulator, the Rag GTPases and the v-ATPase and is necessary for m TORC1 activation by amino acids, particularly arginine.Overexpression of the full-length protein or just its Ragulator-binding domain makes m TORC1 signaling insensitive to amino acid starvation but does not affect its dependence on Rag activity.SLC38A9 reconstituted in proteoliposomes transports arginine, an abundant amino acid in the lysosome and necessary for m TORC1 pathway activity.These results place SLC38A9 between amino acids and the Rag GTPases and are consistent with the notion that amino acids are sensed at the lysosome.Our group has been interested in amino acid similarity in the context of peptides binding to proteins.Given binding data for several peptide ligands, the challenge is to predict the affinity of any peptide of arbitrary sequence.Net MHC is trained using a BLOSUM matrix based encoding of peptide sequences [8–13].This provides the neural network with information on amino acid similarity, and allows it to predict the impact of residues on binding that are not represented in the training set. Given that m TORC1 regulates a multitude of processes, it is not surprising that the pathway it anchors is deregulated in various common diseases, including cancer. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. The m TORC1 kinase is a master growth regulator that responds to numerous environmental cues, including amino acids, to regulate many processes, such as protein, lipid, and nucleotide synthesis, as well as autophagy.