Fig. 1: Physics of sequence-dependent IDR association and partitioning illustrated by an intuitive sliding-sequence consideration.
A Schematics of interactions between an IDR scaffold (red chains) and an IDR client (blue chains) in and around a condensate (green area), wherein amino acid residues at selected positions along the two IDR sequences are represented by symbols of different shapes and colors. The dotted circles highlight several possible configurations of inter-chain interactions between the IDR sequences: (1) Because of chain connectivity, it is physically plausible for contact-like interactions to exist between chains that are locally approximately aligned; (2) in the condensed phase, these locally aligned contact-like interactions can be between different pairs of chains at different sequence positions; and (3) the local alignments can be parallel or antiparallel with respect to the N- to C-terminus directions of the two IDRs. (4,5) More generally, it is also possible that some chain segments of either IDR may not be interacting in close spatial proximity with another IDR, especially when the segments are outside the condensed phase, and that (6) some contact-like interactions may not involve locally aligned chain segments at all. B The sliding-sequence analysis in the present work entails determination of interaction energies as the client sequence (blue) is moved along the scaffold sequence (red) as indicated by the double arrows. Three examples of different relative positions of the two sequences are schematically depicted in parallel as well as in antiparallel alignments (a,b). C Simple 8-bead model sequences each with four electric charges. Positive and negative charges are represented, respectively, by blue and red beads in the inset. The interaction of each of the three model client sequences (marked by blue, light blue, and green lines in the inset) with the model scaffold sequence (red line) is assessed by \({U}_{{ij}}/{k}_{{{\rm{B}}}}T\) (potential energy given by Eq.6 in units of kBT, vertical variable) as a function of the distance between the centers of the client and scaffold sequences (horizontal variable). The \({U}_{{ij}}/{k}_{{{\rm{B}}}}T\) energy profiles (curves) and the Boltzmann-weighted average energies \(\langle {U}_{{ij}}\rangle /{k}_{{{\rm{B}}}}T\) (horizontal dashed lines) are shown using the same color code for the clients as that in the inset. D IDRs with a blockier charge pattern interact more favorably with the IDR of MED1. As in (C), the vertical variable is \({U}_{{ij}}/{k}_{{{\rm{B}}}}T\) and the horizontal variable is the distance between the centers of the MED1 and the NELFE or SPT6 IDR sequence. Positively and negatively charged residues are indicated by blue and red lines in the depiction of the MED1 and IDR sequences (bottom, with the N and C termini marked). The NELFE and SPT6 sequences are shown in their respective positions at which the interaction with MED1 is most favorable (most negative energies marked by circles along the orange and blue curves). Each of the dotted lines (same color code for the IDRs) is the arithmetic mean of the screened Coulomb energy (vertical variable) over the horizontal range; the thicker dashed curves are the Boltzmann-weighted average energies \(\langle {U}_{{ij}}\rangle /{k}_{{{\rm{B}}}}T\). Each of the energy profiles provided in (C) and (D) is for the alignment that has the lowest energy minimum. For presentational consistency, each of the averaged energies marked by the horizontal dashed and dotted lines is computed using the corresponding shown energy profile without contributions from the energy profile for the opposite alignment.
