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Amino acid distribution rules predict protein fold: protein grammar for beta-strand sandwich-like structures.

Kister A - Biomolecules (2015)

Bottom Line: The advantage of the proposed approach is that it does not require that query proteins have a high degree of homology to proteins with known structure.Another advantage of our approach is that it allows for a better understanding of which residues play an essential role in protein fold formation.It may, therefore, facilitate rational protein engineering design.

View Article: PubMed Central - PubMed

Affiliation: Department of Mathematics, Rutgers University, Piscataway, NJ 08854, USA. akister@math.rutgers.edu.

ABSTRACT
We present an alternative approach to protein 3D folding prediction based on determination of rules that specify distribution of "favorable" residues, that are mainly responsible for a given fold formation, and "unfavorable" residues, that are incompatible with that fold, in polypeptide sequences. The process of determining favorable and unfavorable residues is iterative. The starting assumptions are based on the general principles of protein structure formation as well as structural features peculiar to a protein fold under investigation. The initial assumptions are tested one-by-one for a set of all known proteins with a given structure. The assumption is accepted as a "rule of amino acid distribution" for the protein fold if it holds true for all, or near all, structures. If the assumption is not accepted as a rule, it can be modified to better fit the data and then tested again in the next step of the iterative search algorithm, or rejected. We determined the set of amino acid distribution rules for a large group of beta sandwich-like proteins characterized by a specific arrangement of strands in two beta sheets. It was shown that this set of rules is highly sensitive (~90%) and very specific (~99%) for identifying sequences of proteins with specified beta sandwich fold structure. The advantage of the proposed approach is that it does not require that query proteins have a high degree of homology to proteins with known structure. So long as the query protein satisfies residue distribution rules, it can be confidently assigned to its respective protein fold. Another advantage of our approach is that it allows for a better understanding of which residues play an essential role in protein fold formation. It may, therefore, facilitate rational protein engineering design.

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Disallowed arrangement of strands 1, 2 and 3 in a beta sheet because of loops overlapping.
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biomolecules-05-00041-f002: Disallowed arrangement of strands 1, 2 and 3 in a beta sheet because of loops overlapping.

Mentions: In Figure 1, strands 3 and 4 are at the right edges of respective beta-sheets, and strands 1 and 7, at the left edge (strands 1 and 7 are consecutive in cyclic ordering). For the most part, these constraints are the consequence of a general structural rule for proteins–avoidance of energetically unfavorable loop overlapping (Figure 2) [36].


Amino acid distribution rules predict protein fold: protein grammar for beta-strand sandwich-like structures.

Kister A - Biomolecules (2015)

Disallowed arrangement of strands 1, 2 and 3 in a beta sheet because of loops overlapping.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4384110&req=5

biomolecules-05-00041-f002: Disallowed arrangement of strands 1, 2 and 3 in a beta sheet because of loops overlapping.
Mentions: In Figure 1, strands 3 and 4 are at the right edges of respective beta-sheets, and strands 1 and 7, at the left edge (strands 1 and 7 are consecutive in cyclic ordering). For the most part, these constraints are the consequence of a general structural rule for proteins–avoidance of energetically unfavorable loop overlapping (Figure 2) [36].

Bottom Line: The advantage of the proposed approach is that it does not require that query proteins have a high degree of homology to proteins with known structure.Another advantage of our approach is that it allows for a better understanding of which residues play an essential role in protein fold formation.It may, therefore, facilitate rational protein engineering design.

View Article: PubMed Central - PubMed

Affiliation: Department of Mathematics, Rutgers University, Piscataway, NJ 08854, USA. akister@math.rutgers.edu.

ABSTRACT
We present an alternative approach to protein 3D folding prediction based on determination of rules that specify distribution of "favorable" residues, that are mainly responsible for a given fold formation, and "unfavorable" residues, that are incompatible with that fold, in polypeptide sequences. The process of determining favorable and unfavorable residues is iterative. The starting assumptions are based on the general principles of protein structure formation as well as structural features peculiar to a protein fold under investigation. The initial assumptions are tested one-by-one for a set of all known proteins with a given structure. The assumption is accepted as a "rule of amino acid distribution" for the protein fold if it holds true for all, or near all, structures. If the assumption is not accepted as a rule, it can be modified to better fit the data and then tested again in the next step of the iterative search algorithm, or rejected. We determined the set of amino acid distribution rules for a large group of beta sandwich-like proteins characterized by a specific arrangement of strands in two beta sheets. It was shown that this set of rules is highly sensitive (~90%) and very specific (~99%) for identifying sequences of proteins with specified beta sandwich fold structure. The advantage of the proposed approach is that it does not require that query proteins have a high degree of homology to proteins with known structure. So long as the query protein satisfies residue distribution rules, it can be confidently assigned to its respective protein fold. Another advantage of our approach is that it allows for a better understanding of which residues play an essential role in protein fold formation. It may, therefore, facilitate rational protein engineering design.

Show MeSH