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Here we describe a motif-based method to computationally design protein-protein complexes with native-like interface composition and interaction density.
The static metrics measure complexity and criticality of component assembly, wherein complexity is measured using Component Packing Density and Component Interaction Density metrics.
This problem with "interaction density" is general to explicit numerical methods –it is not unique to the PAIRS approach.
Given knowledge of a maximum expected interaction density a constant and conservative fraction of the force in equation 3 could be applied over any time-step.
Alternatively, one might adopt a scheme to actively determine the interaction density at each time-step and attenuate the force in equation 3 accordingly, i.e. an adaptive PAIRS coefficient scheme.
Hansen and Wagner [18] showed that higher-order genetic interactions are potentially important if the total genomic mutation rate is large and the interaction density among loci is not too low.
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We define an alternative measure for the tendency to interact with proteins of a similar age, ΔDnew, based on interaction densities normalized by the age groups' connectivity (see Materials and Methods for more detail).
Binary interaction densities for repeat-unit pairs were evaluated from the lower critical solution temperature type phase behaviour using the lattice-fluid theory of Sanchez and Lacombe and from copolymer composition miscibility boundaries using the Flory-Huggins theory.
Only S3.1 and S3.3 groups have within-group interaction densities close to that of S3.7.
In order to test if the observed density of interactions among S3.7 proteins is expected by chance, we compared within-group interaction densities of the groups with those in 100 randomized instances of the network, and find that S3.7 proteins are significantly more inter-connected than what would be expected by chance (Fig. 2b).
The interaction densities were further normalized according to the overall density for each TG (For interaction densities before normalization, see Additional file 1, Table S1).
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