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UCRL-JRNL-214218 Nonlinearly Additive Forces in Univalent Ligand Binding to a Single Protein Revealed with Force Spectroscopy T. V. Ratio, R. E. Rudd, K. C. Angry, R. L. Balloon, M. W. Refresh August
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Responsibility for any of the work herein does not lie solely on the user or user's employer. This document is provided here without any warranty. Abstract The structure of a large class of small univalent ligands has been recently determined using computational molecular dynamics. As an example of the type of structure shown, we show that unrelated polypeptides, containing a peptide, protein or RNA loop, exhibit large conformational changes that change their molecular weight by a factor of ~20. This is caused by a large force on the proteins and the RNA strand. We show that this force is due to the conformational change of the univalent ligand, as inferred from the force spectra and by measuring the energy of the resulting conformational change. This structure corresponds to a class of univalent Ligand known as a “dimer,” as it contains multiple univalent Ligands. The main type of dimer (also called a “protein molecule”) is one of the major classes of ligand functionalized with a short segment of a sequence (referred to as the “prime”) for the direct binding of a protein to a peptide. More recently, a few structural studies that have determined the structure of dimer have been published. This paper describes a second class of dimer structures, one composed by a long chain of short peptides, which has been demonstrated not by direct binding, but by indirect structural investigations. The second class of dimer appears to be stable when bound directly to a small protein or RNA, but is also stable when the protein or RNA is not present. The stability of the second class of dimer is independent of its ability to be directly bound by a small protein or RNA strand. Keywords: Dimer, Unrelated peptides, Direct binding, Prolong Chain, Peptide Introduction The structure of small protein molecules, which also includes proteins, RNA and DNA molecules, is important because they are the major structural components of many of our cells. For example, the DNA helix is composed of several linear blocks (DNA molecules), and proteins and RNA are composed of long single molecules, such as amino acids (which also contains a linear structure). It is often stated that the first two principles of biology are: (1) DNA/RNA structure is important; (2) Small, linear molecules are important.

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