The study is aimed at the comparison of homologous protein BLOCKs using different diversity parameters (MDRs, DHPs and MCRs etc) that are formulated using positional frequencies of observed hetero-pairs and homo-pairs of BLOCKs. APBEST, written in AWK programming language, extracts these BLOCK specific parameters. How efficient is the program? Are these parameters correlate with already existing literature reports? To have resolution of these questions, we have implemented the program first on constructed BLOCK FASTA files. Details of itemized results of simulation are presented in Supplimentary Table 1. Sequence variability is the most reliable information to gain insight into BLOCK evolution. Positional ensemble variability of BLOCK is efficiently
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First, overall diversity calculated using frequencies of hetero-pairs in BLOCK (Plot A) follows similar pattern as Shannon Entropy Method (Plot C). Second, diversity profile for substitution by a given residue follows a characteristic pattern (plot B and D). Positional diversity changes when BLOCK undergoes amino acid substitutions. It is maximum when a position in BLOCK, has maximum and fixed occurrence of a residue (here V, first residue) followed by multiple copies of a second one (here I, second residue) with or without others. When other residues replace second residue, its diversity (but not the first one) declines (Plot B and D). Third, diversity of first residue does not change as far as it exceeds others and positional count is fixed. However, it is maximum when half the total positions are occupied by it (data not shown). APBEST identify these residues as maximally diverse residue 1, (MDR1), 2 (MDR2) and 3 (MDR3). Forth, first and second residues (V and I) form dominantly used hetero-pair (DHP). Similar to MDRs, APBEST identify these as DHP1, DHP2 and DHP3. Using the same principle, maximally conserved residues are extracted as MCR1, MCR2 and MCR3 (Table …show more content…
An integrated view of protein evolution. Nature Reviews Genetics. 2006 May 1;7(5):337-48.] of which function is closely related with amino acid substitutions [Ng and Henikoff, 2006]. To explore further in these aspects, we have analyzed thirty homologous protein BLOCKs of known divergence rate with the help of APBEST. Protein BLOCKs used in the study are supplied as downloadable material along with (download from: https://sourceforge.net/projects/apbest/files/) details on FASTA file name, BLOCK-width, number of sequences per BLOCK, mean properties such as , , , , of sequence segments in BLOCKs, PDB file used for assessment of secondary structure (supplementary table 1). The table also details on normalized positions for invariant, only hydrophobic, only hydrophilic, mixed (hydrophobic and hydrophilic) positions and Shannon entropy conservation. In these qualitative analyses, it was seen that a) majority of positions in BLOCKs contains mixed type (HB plus HL) amino acids. Thus, HB plus HLdominate over others such as HB-HB, PU+PC etc. b). All but myoglobin and carbonic anhydrase C contains invariant lines with highest for corticotrophin BLOCK. Invariant line doesn’t evolve over time and are largely involved in the preservation of structure and or function of BLOCK as parental one. c) Shannon entropy is the measure of positional conservation. A value ≤1.0 indicate highly conserved positions. Details
First, overall diversity calculated using frequencies of hetero-pairs in BLOCK (Plot A) follows similar pattern as Shannon Entropy Method (Plot C). Second, diversity profile for substitution by a given residue follows a characteristic pattern (plot B and D). Positional diversity changes when BLOCK undergoes amino acid substitutions. It is maximum when a position in BLOCK, has maximum and fixed occurrence of a residue (here V, first residue) followed by multiple copies of a second one (here I, second residue) with or without others. When other residues replace second residue, its diversity (but not the first one) declines (Plot B and D). Third, diversity of first residue does not change as far as it exceeds others and positional count is fixed. However, it is maximum when half the total positions are occupied by it (data not shown). APBEST identify these residues as maximally diverse residue 1, (MDR1), 2 (MDR2) and 3 (MDR3). Forth, first and second residues (V and I) form dominantly used hetero-pair (DHP). Similar to MDRs, APBEST identify these as DHP1, DHP2 and DHP3. Using the same principle, maximally conserved residues are extracted as MCR1, MCR2 and MCR3 (Table …show more content…
An integrated view of protein evolution. Nature Reviews Genetics. 2006 May 1;7(5):337-48.] of which function is closely related with amino acid substitutions [Ng and Henikoff, 2006]. To explore further in these aspects, we have analyzed thirty homologous protein BLOCKs of known divergence rate with the help of APBEST. Protein BLOCKs used in the study are supplied as downloadable material along with (download from: https://sourceforge.net/projects/apbest/files/) details on FASTA file name, BLOCK-width, number of sequences per BLOCK, mean properties such as , , , , of sequence segments in BLOCKs, PDB file used for assessment of secondary structure (supplementary table 1). The table also details on normalized positions for invariant, only hydrophobic, only hydrophilic, mixed (hydrophobic and hydrophilic) positions and Shannon entropy conservation. In these qualitative analyses, it was seen that a) majority of positions in BLOCKs contains mixed type (HB plus HL) amino acids. Thus, HB plus HLdominate over others such as HB-HB, PU+PC etc. b). All but myoglobin and carbonic anhydrase C contains invariant lines with highest for corticotrophin BLOCK. Invariant line doesn’t evolve over time and are largely involved in the preservation of structure and or function of BLOCK as parental one. c) Shannon entropy is the measure of positional conservation. A value ≤1.0 indicate highly conserved positions. Details