The contact order of a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

is a measure of the locality of the inter-

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...

contacts in the protein's native state

tertiary structure Protein tertiary structure is the three dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains may i ...

. It is calculated as the average sequence distance between residues that form

native contact In protein folding, a native contact is a contact between the side chains of two amino acids that are not neighboring in the amino acid sequence (i.e., they are more than four residues apart in the primary sequence in order to remove trivial i to ...

s in the folded protein divided by the total length of the protein. Higher contact orders indicate longer folding times, and low contact order has been suggested as a predictor of potential downhill folding, or protein folding that occurs without a free energy barrier. This effect is thought to be due to the lower loss of

conformational entropy In chemical thermodynamics, conformational entropy is the entropy associated with the number of conformations of a molecule. The concept is most commonly applied to biological macromolecules such as proteins and RNA, but also be used for poly ...

associated with the formation of local as opposed to nonlocal contacts. Relative contact order (CO) is formally defined as: :

CO=\sum^\Delta S_

where ''N'' is the total number of contacts, Δ''Si,j'' is the sequence separation, in residues, between contacting residues ''i'' and ''j'', and ''L'' is the total number of residues in the protein. The value of contact order typically ranges from 5% to 25% for single-domain proteins, with lower contact order belonging to mainly helical proteins, and higher contact order belonging to proteins with a high beta-sheet content.

Protein structure prediction Protein structure prediction is the inference of the three-dimensional structure of a protein from its amino acid sequence—that is, the prediction of its secondary and tertiary structure from primary structure. Structure prediction is different ...

methods are more accurate in predicting the structures of proteins with low contact orders. This may be partly because low contact order proteins tend to be small, but is likely to be explained by the smaller number of possible long-range residue-residue interactions to be considered during

global optimization Global optimization is a branch of applied mathematics and numerical analysis that attempts to find the global minima or maxima of a function or a set of functions on a given set. It is usually described as a minimization problem because the max ...

procedures that minimize an energy function.Mount DM. (2004). ''Bioinformatics: Sequence and Genome Analysis'' 2nd ed. Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY. Even successful structure prediction methods such as the

Rosetta Rosetta or Rashid (; ar, رشيد ' ; french: Rosette ; cop, ϯⲣⲁϣⲓⲧ ''ti-Rashit'', Ancient Greek: Βολβιτίνη ''Bolbitinē'') is a port city of the Nile Delta, east of Alexandria, in Egypt's Beheira governorate. The Ro ...

method overproduce low-contact-order structure predictions compared to the distributions observed in experimentally determined protein structures. The percentage of the natively folded contact order can also be used as a measure of the "nativeness" of folding

transition state In chemistry, the transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the state corresponding to the highest potential energy along this reaction coordinate. It is often marked ...

Phi value analysis Phi value analysis, \phi analysis, or \phi-value analysis is an experimental protein engineering technique for studying the structure of the folding transition state of small protein domains that fold in a two-state manner. The structure of the f ...

in concert with

molecular dynamics Molecular dynamics (MD) is a computer simulation method for analyzing the physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a fixed period of time, giving a view of the dynamic "evolution" of t ...

has produced transition-state models whose contact order is close to that of the folded state in proteins that are small and fast-folding. Further, contact orders in transition states as well as those in native states are highly correlated with overall folding time. In addition to their role in structure prediction, contact orders can themselves be predicted based on a sequence alignment, which can be useful in classifying the fold of a novel sequence with some degree of homology to known sequences.{{cite journal , last1 = Shi , first1 = Yi , last2 = Zhou , first2 = Jianjun , last3 = Arndt , first3 = David , author4-link=David S. Wishart , last4 = Wishart , first4 = David S. , last5 = Lin , first5 = Guohui , year = 2008 , title = Protein contact order prediction from primary sequences , journal = BMC Bioinformatics , volume = 9 , page = 255 , doi=10.1186/1471-2105-9-255, pmid = 18513429 , pmc = 2440764

References

Bioinformatics Protein structure

See also

References