PFVM for P53 protein
The protein of Human Cellular tumor antigen p53(P53_HUMAN)is another
sample to illustrate how the local folding variations in PFVM correlate
with the order of amino acid along sequence. The p53 involves many
mechanisms for anticancer functions and plays a role in apoptosis,
genomic stability, and inhibition of angiogenesis. The human TP53 gene
encodes 9 of protein isoforms11Surget S, Khoury MP, Bourdon JC,
”Uncovering
the role of p53 splice variants in human malignancy: a clinical
perspective”. OncoTargets and Therapy. 7: 57–68, (2013)., and the
canonical sequence of isoform p53-alpha with 393 amino acids is
available in UniProt database. According the sequence, the PFVM of
P53_HUMAN protein is obtained and shown in Table 3. Although the
protein of p53-alpha for human has 393 amino acids in sequence, the PFVM
of p53-alpha was acquired within one minute using a personal computer.
First, the PFVM directly displayed the fluctuation of local folding
variations along the sequence. For examples, some sets of 5 successive
amino acids have only one folding shape representing with one PFSC
letter in PFVM, such as fragments in sequence of “DEAPR” (61-65),
“EAPRM” (62-66), “APSWP” (88-92), “PSWPL” (89-93), “NKMFC”
(131-135) and “KMFCQ” (132-136) etc. Some sets of 5 successive amino
acids have more folding shapes representing with higher number of PFSC
letters in PFVM, such as “PLSQE” (13-17) has 14 folding shapes;
“SDGLA” (185-189) has 13; “SSGNL” (260-264) 15 and “SKKGQ”
(371-375) 16 etc. Second, the pattern of folding variations of
P53_HUMAN in PFVM showed many regions agree with the disorder
determined by PDB which is displayed on the bottom of Table 3. For
examples, regions of 20-25, 124-136, 230-241 and 332-347 have less
variations and disorder. However, the PFVM may exposed the folding
variations more detail. Third, all possible conformations for the
p53-alpha protein can be constructed by various combinations with taking
one PFSC letter from each column in PFVM. Actually, with PFVM, an
astronomical number of folding conformations for the p53-alpha protein
can be constructed and represented by 2.008x10270 of
PFSC strings. It showed that the astronomical number of all possible
conformations for p53-alpha protein were not vague anymore because the
number can be explicitly calculated based on PFVM.