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Although it would not be appropriate to generalize from the single example of AP, our dissection of the AP active site network does show that optimal positioning of catalytic residues can occur with only a subset of the full network; thus, it may be possible to attempt designs with active site modules that correspond to functional units identified in this study and, we hope, subsequent studies.
We have synthesized peptides, called core modules, that correspond to the elements of secondary structure that carry the very slowest exchanging amides in a protein.
The project includes three complementary modules that correspond to various steps in medical care [ 20].
This approach was used to reveal 44 modules that correspond to several metabolic pathways in C. elegans, including lipid and amino acid biosynthesis [ 7].
Table 5 shows 12 interaction modules that correspond to the most specific (lowest level) GO annotations of all identified interaction modules.
Since the goal of alignment is to extract modules that correspond to specific biological processes, we examined the use of functional similarity of proteins across networks to aid alignment.
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We have developed an approach that identifies nodes in a network responsible for interactions between modules that potentially correspond to genes regulating crosstalk between pathways represented by these modules.
The communality analysis provides a better topology description of the network including the location of highly connected sub-graphs (cliques) and/or overlapping modules that usually correspond with relevant biological information.
Our analysis identified two sub-modules that correspond to two distinct stages in this process: one module (ESP-97) involves genes encoding proteins that transfer mannose residues to the nascent chain, and the second module (ESP-96) involves genes that subsequently transfer glucose residues to the nascent chain (Helenius and Aebi, 2004).
The Ingenuity Pathways Analysis application (IPA) was used to organize the disease-associated genes into networks of interaction and to find modules of functionally related genes that correspond to pathways as previously described [ 7].
According to this and other studies (e.g. [ 6]) the outputs of these modules (i.e. attractors that correspond to the possible alternative multigene expression profiles) are highly robust in the face of diverse perturbations, suggesting that these may act as patterning modules for a wide range of parameter values in kinetic functions of the network.
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