Unambiguous assignment of kinked‐ <i>β</i> sheets leads to insights into molecular grammar of reversibility in biomolecular condensates

Kinked- <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:mrow><mml:mi>β</mml:mi></mml:mrow> <mml:annotation>$$ \beta $$</mml:annotation></mml:semantics> </mml:math> sheets are short peptide motifs that appear as distortions in <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:mrow><mml:mi>β</mml:mi></mml:mrow> <mml:annotation>$$ \beta $$</mml:annotation></mml:semantics> </mml:math> strands and often mediate formation of reversible amyloid fibrils in prion-like proteins. Standard methods for assigning secondary structures cannot distinguish these esoteric motifs. Here, we provide a supervised machine learning-based structural quantification map to unambiguously characterize kinked- <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:mrow><mml:mi>β</mml:mi></mml:mrow> <mml:annotation>$$ \beta $$</mml:annotation></mml:semantics> </mml:math> sheets from coordinate data. We find that these motifs, although deviating from standard <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:mrow><mml:mi>β</mml:mi></mml:mrow> <mml:annotation>$$ \beta $$</mml:annotation></mml:semantics> </mml:math> strand region of the Ramachandran plot, scatter around the allowed regions. We also demonstrate the applicability of our technique in wresting out LARKS, which are kinked- <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:mrow><mml:mi>β</mml:mi></mml:mrow> <mml:annotation>$$ \beta $$</mml:annotation></mml:semantics> </mml:math> strands with designated sequence. Additionally, from our exhaustive simulation generated conformations, we create a repository of potential kinked peptide-segments that can be used as a screening-library for assigning <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:mrow><mml:mi>β</mml:mi></mml:mrow> <mml:annotation>$$ \beta $$</mml:annotation></mml:semantics> </mml:math> kinks in unresolved coordinate dataset. Overall, our map for kinked- <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:mrow><mml:mi>β</mml:mi></mml:mrow> <mml:annotation>$$ \beta $$</mml:annotation></mml:semantics> </mml:math> provides a robust framework for detailed structural and kinetics investigation of these important motifs in prion-like proteins that lead to formation of amyloid fibrils.