Reduction of protein sequence complexity by residue grouping

Abstract

It is well known that there are some similarities among various naturally occurring amino acids. Thus, the complexity in protein systems could be reduced by sorting these amino acids with similarities into groups and then protein sequences can be simplified by reduced alphabets. This paper discusses how to group similar amino acids and whether there is a minimal amino acid alphabet by which proteins can be folded. Various reduced alphabets are obtained by reserving the maximal information for the simplified protein sequence compared with the parent sequence using global sequence alignment. With these reduced alphabets and simplified similarity matrices, we achieve recognition of the protein fold based on the similarity score of the sequence alignment. The coverage in dataset SCOP40 for various levels of reduction on the amino acid types is obtained, which is the number of homologous pairs detected by program BLAST to the number marked by SCOP40. For the reduced alphabets containing 10 types of amino acids, the ability to detect distantly related folds remains almost at the same level as that by the alphabet of 20 types of amino acids, which implies that 10 types of amino acids may be the degree of freedom for characterizing the complexity in proteins.

Simplification of complexity in protein molecular systems by grouping amino acids: a view from physics

“…Through the maximization of S, a series of optimal groupings could be obtained (as shown in Figure 5). It is interesting that the HP grouping determined with BLOSUM62 matrix is same as that from the interaction [102]. This consistency further confirms that the HP grouping is a fundamental feature of protein systems, and also demonstrates the correctness of these grouping methods which precisely characteristics of protein systems.…”

“…The simplified groups which maximizes the information in simplified sequences. Note: Generated based on the data from [102].…”

“…While further considering the dynamic and functional behaviors, 8-10 groups of amino acids would be necessary [50,79,90,92,93,102,[119][120][121]. Together with all these considerations, the minimal set to fulfill various kinds of biological functions might be the alphabet with 10 amino acids, which are verified with sequence design and homolog recognition [79,93,102,105,110,122]. This measures the possible complexity of protein systems.…”

A Systematic and Comprehensive Combinatorial Approach to Simultaneously Improve the Activity, Reaction Specificity, and Thermal Stability of p-Hydroxybenzoate Hydroxylase

“…Usually, iterative selection and combination can greatly reduce the redundancy of the sequence space (45)(46)(47)(48)(49). Based on the properties of all the purified single mutant proteins as to each Cys and Met site and assuming strict additivity, the number of mutants expected to be more active than the wild type in terms of the main activity value is estimated to be 8.9 ϫ 10 7 (ϭ 4 (number of mutants with higher main activity than the wild type at Cys-152) ϫ 2 (at Cys-158), ϫ 4 (at Cys-211), ϫ 3 (at Cys-332), ϫ 6 (at Met-52), ϫ 3 (at Met-65), ϫ 5 (at Met-98), ϫ 6 (at Met-110), ϫ 7 (at Met-213), ϫ 5 (at Met-276), ϫ 7 (at Met-346), and ϫ 7 (at Met 349)).…”

Multiple Sequence Alignment Based on Set Covers

“…The most familiar scenario for the use of set covers is the case of R as a set of amino acids, so henceforth we concentrate mainly on multiple protein alignments, even though it makes perfect sense for R to be a set of nucleotides as well. Set covers of an amino-acid alphabet have been studied extensively, as for example in [50,20,53,48,28,32,24,36,52,66,19,5,27].…”