The focus of network designers in the area of backbone design is on the choice of routing and switching equipment, the wide area protocols to implement, and the initial cost of the system.
Intra building backbone design between main cross connect (MC) or intermediate cross-connect (IC), and the horizontal cross-connect (HC) is usually straightforward.
We find that such a flexible backbone design method better recapitulates protein family sequence variation than sequence optimization on fixed backbones or randomly perturbed backbone ensembles for ten diverse protein structures.
In another paper, we presented a new combinatorial backbone design algorithm AbDesign where the fuzzy-logic framework was used to optimize protein backbones and sequences for both stability and binding affinity in antibody-design simulation.
The approach decomposes the SND problem into two subproblems, Backbone design and Access design, and uses an iterative multi-stage method for solving the SND problem in a hierarchical fashion.
The rational design of protein protein interactions from scratch is still an unsolved problem, but recent developments in flexible backbone design and energy functions hold promise for the future.
However, when redesigning naturally occurring protein structures, most fixed backbone design algorithms return amino acid sequences that share strong sequence identity with wild-type sequences, especially in the protein core.
Comparison with phage display and other experimental data suggests that the peptide extension approach recapitulates naturally occurring peptide binding specificity better than fixed backbone design, and that it should be useful for predicting peptide binding specificities from crystal structures.
Incorporating functional constraints into flexible backbone design should help to achieve challenging engineering goals that exploit the role of conformational variability in controlling biological processes, while more generally advancing biophysical understanding of the relationship between variations in protein sequence, structure, dynamics, and function.
Both TU/pg and TU/RNA estimate the specific activity and correlate well with improved lentiviral vector backbone design.
