The circuit topology of a folded linear
polymer
A polymer (; Greek '' poly-'', "many" + '' -mer'', "part")
is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...
refers to the arrangement of its intra-molecular contacts. Examples of linear polymers with intra-molecular contacts are
nucleic acid
Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main ...
s and
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 ...
s. Proteins fold via formation of contacts of various nature, including hydrogen bonds, disulfide bonds, and beta-beta interactions. Contacts in the genome are established via protein bridges including
CTCF and
cohesin
Cohesin is a protein complex that mediates sister chromatid cohesion, homologous recombination, and DNA looping. Cohesin is formed of SMC3, SMC1, SCC1 and SCC3 ( SA1 or SA2 in humans). Cohesin holds sister chromatids together after DNA rep ...
s and are measured by technologies including
Hi-C. Circuit topology categorises the topological arrangement of these physical contacts, that are referred to as hard contacts. Furthermore, chains can fold via knotting (or formation of "soft" contacts). Circuit topology uses a similar language to categorise both "soft" and "hard" contacts, and provides a full description of a folded linear chain.
A simple example of a folded chain is a chain with two hard contacts. For a chain with two binary contacts, three arrangements are available: parallel, series and crossed. For a chain with n contacts, the topology can be described by an n by n matrix in which each element illustrates the relation between a pair of contacts and may take one of the three states, P, S and X. Multivalent contacts can also be categorised in full or via decomposition into several binary contacts. Similarly, circuit topology allows for classification of the pairwise arrangements of chain crossings and tangles, thus providing a complete 3D description of folded chains.
Circuit topology has implications for folding kinetics and
molecular evolution
Molecular evolution is the process of change in the sequence composition of cellular molecules such as DNA, RNA, and proteins across generations. The field of molecular evolution uses principles of evolutionary biology and population genet ...
and has been applied to engineer polymers including protein origami. Circuit topology along with contact order and size are determinants of folding rate of linear polymers. The topology of the cellular proteome and natural RNA reflect evolutionary constraints on biomolecular structures. Topology landscape of biomolecules can be characterized and evolution of molecules can be studied as transition pathways within the landscape.
Further reading
* B. Scalvini et al., Circuit topology analysis of cellular genome reveals signature motifs, conformational heterogeneity, and scaling. iScience (2022)
link
* B. Scalvini et al., Topological principles of protein folding. PCCP (2021)
link* A. Golovnev at el., Generalized circuit topology of folded linear chains. iScience (2020)
link* M. Heidari et al., Circuit topology analysis of polymer folding reactions. ACS Central Science (2020
link
References
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See also
*
Molecular topology
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...
Molecular topology
Molecular geometry
Supramolecular chemistry
Topology
Mathematical chemistry