Structural biology: A toolbox for protein design

  title={Structural biology: A toolbox for protein design},
  author={Birte H{\"o}cker},
Some of the principles underlying how amino-acid sequences determine the three-dimensional structures of proteins have been defined. This has enabled a successful approach to designing protein folds from scratch. See Article p.222 When natural proteins folds to produce their unique biologically adapted structure, they do so despite the many energetically unfavorable non-ideal features — such as kinked helices, strained loops and buried polar groups — that arise in proteins as a result of… 
Evolutionary relationship of two ancient protein superfolds.
Evidence of homology between proteins of two ancient and highly populated protein folds, the (βα)8-barrel and the flavodoxin-like fold are found and what is to the authors' knowledge the first representative crystal structure of one of its members is determined, giving new insights into the evolutionary link of two of the earliest folds.
Role of loops connecting secondary structure elements in the stabilization of proteins isolated from thermophilic organisms
The results suggest that β‐hairpins of proteins from thermophilic organisms are very frequently characterized by shortenings of the loops, and this shortening leads to states that display a very strong preference for the most common connectivity of the strands observed in native protein hairpins.
A Computational Framework for Interacting with Physical Molecular Models of the Polypeptide Chain
A flexible, scaled, physical model of the polypeptide chain, which accurately reproduces the bond rotational degrees-of-freedom in the peptide backbone is reported, which can serve as the basis for linking tangible bio-macromolecular models directly to the vast array of existing computational tools to provide an enhanced and interactive human-computer interface.
Structural Bridges through Fold Space
This paper constructs networks that describe global relationships between folds in the form of structural bridges and identifies four highly central pivotal folds representing dominant topological features which act as key attractors within the authors' landscapes.
Computational protein design of ligand binding and catalysis.
Critical Role of a Loop at C-Terminal Domain on the Conformational Stability and Catalytic Efficiency of Chondroitinase ABC I
This study involves manipulation of interactions around Asp689 as a key residue in the central region of the loop containing residues 681–695 located at C-terminal domain of chondroitinase ABC I.
Improving the Anti-Toxin Abilities of the CMG2-Fc Fusion Protein with the Aid of Computational Design
This study shows that the computational design of the PA binding interface of CMG2 to obtainCMG2-Fc variants with improving anti-toxin abilities is viable and demonstrates that computational design can be further applied to generate other CMG 2- Fc mutants with greatly improved therapeutic efficacy.
Physical Biomodeling: a new field enabled by 3-D printing in biomodeling
This work explores a new domain of precision physical modeling at the intersection of experimental data, computational biology and physical modeling for study of biological systems, such as protein folding at nano-scale, with 3D printing techniques.


Principles for designing ideal protein structures
An approach to designing ideal protein structures stabilized by completely consistent local and non-local interactions is described, based on a set of rules relating secondary structure patterns to protein tertiary motifs, which make possible the design of funnel-shaped protein folding energy landscapes leading into the target folded state.
Design of a Novel Globular Protein Fold with Atomic-Level Accuracy
A general computational strategy that iterates between sequence design and structure prediction to design a 93-residue α/β protein called Top7 with a novel sequence and topology, found experimentally to be folded and extremely stable.
Protein folding funnels: a kinetic approach to the sequence-structure relationship.
Monte Carlo simulations demonstrate that folding funnel calculations accurately predict the fact of and the pathways involved in folding-specific sequences, and suggest that geometrically related families of stable, collapsed conformers fulfill kinetic and thermodynamic requirements of protein folding.
Computational design of ligand binding is not a solved problem
It is concluded that although the computational prediction of side-chain conformations appears to be working, it does not necessarily confer binding as expected, and the computational design of ligand binding is not a solved problem and needs to be revisited.
Design of a switchable eliminase
The interplay of protein folding energetics and functional group tuning to convert calmodulin (CaM), a regulatory binding protein, into AlleyCat, an allosterically controlled eliminase is demonstrated.
Kemp elimination catalysts by computational enzyme design
The computational design of eight enzymes that use two different catalytic motifs to catalyse the Kemp elimination—a model reaction for proton transfer from carbon—with measured rate enhancements of up to 105 and multiple turnovers are described.
An exciting but challenging road ahead for computational enzyme design
  • D. Baker
  • Biology
    Protein science : a publication of the Protein Society
  • 2010
This essay compares the activities of de novo designed enzymes to those of naturally occurring enzymes and highlights the considerable challenges which must be overcome for computational design to produce enzymes with levels of activity similar to Those of Naturally occurring enzymes.