Learning to Speak the Language of Proteins

  title={Learning to Speak the Language of Proteins},
  author={David T. Jones},
  pages={1347 - 1348}
Structural biologists have spent decades pondering the protein-folding problem, which seeks to explain how a simple string of amino acids self-assembles into a complex three-dimensional folded protein. In his Perspective, Jones explores progress in this arena, discussing the leap forward made by Kuhlman et al. These investigators have designed a protein from scratch on the computer and then synthesized and analyzed it in atomic detail using x-ray crystallography and NMR spectroscopy. The… Expand
Molecular Embodiments and the Body-work of Modeling in Protein Crystallography
This ethnographic study of protein crystallography shows that becoming an expert crystallographer, and so making sense of such intricate objects, requires researchers to draw on their bodies as a resource to learn about, work with, and communicate precise molecular configurations. Expand
Understanding the folding and stability of a zinc finger‐based full sequence design protein with replica exchange molecular dynamics simulations
The results show that the folding of the FSD‐1 is initiated by the hydrophobic collapse, which is accompanied with the formation of the C‐terminal α‐helix, which has much higher stability than the β‐hairpin. Expand
Using machine learning for decoy discrimination in protein tertiary structure prediction
This thesis has demonstrated the feasibility of using machine learning, more specifically neural networks, in the problem of decoy discrimination, and evolutionary information in the form of PSI-BLAST profiles has been success fully used to further improve decoydiscrimination, particularly in the discrimination of native structures. Expand
GaN photonic-crystal surface-emitting laser
Summary form only given. Recently, there has been growing interest in photonic-crystal surface-emitting lasers (PC-SELs) (1-4). The lasing principle exploited by the lasers is based on the band-edgeExpand
Diseño, síntesis y estructura de dominios helicoidales. Influencia de la introducción de aminoácidos D.
Tesis del Departament de Quimica Organica de la Universitat de Barcelona (UB).-- Fecha de defensa 16-01-2008.


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. Expand
Inverse protein folding problem: designing polymer sequences.
  • K. Yue, K. Dill
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1992
This work designs the hydrophobicity of proteins using a model of self-avoiding hydrophobic/polar chains on two-dimensional square lattices and shows that some design strategies produce good sequences and scale only linearly with chain length. Expand
High-resolution protein design with backbone freedom.
The de novo design of a family of alpha-helical bundle proteins with a right-handed superhelical twist is described, where the overall protein fold was specified by hydrophobic-polar residue patterning, whereas the bundle oligomerization state, detailed main-chain conformation, and interior side-chain rotamers were engineered by computational enumerations of packing in alternate backbone structures. Expand
Protein superfamilles and domain superfolds
A classification is considered that extends the sequence-based superfamilies to include proteins with similar function and three-dimensional structures but no sequence similarity, which has implications for protein-fold recognition. Expand
De novo protein design: fully automated sequence selection.
The first fully automated design and experimental validation of a novel sequence for an entire protein is described, and a BLAST search shows that the designed sequence, full sequence design 1 (FSD-1), has very low identity to any known protein sequence. Expand
One fold with many functions: the evolutionary relationships between TIM barrel families based on their sequences, structures and functions.
The eightfold barrel structure, first observed in triose-phosphate isomerase, occurs ubiquitously in nature and is an extreme example of the "one fold-many functions" paradigm, which illustrates the difficulty of assigning function through a structural genomics approach for some folds. Expand
Tertiary templates for proteins. Use of packing criteria in the enumeration of allowed sequences for different structural classes.
The preliminary tests reported here make it appear likely that templates prepared from the currently known core structures will be able to discriminate between these structures, and an algorithm to supply a list of permitted sequences of internal residues compatible with a known core structure is developed. Expand
Protein structure prediction in 2002.
Although sequence/structure alignment remains the bottleneck in comparative modeling, there has been substantial progress in fully automated remote homolog detection and in de novo structure prediction. Expand
Enzyme-like proteins by computational design
  • D. Bolon, S. L. Mayo
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2001
The development and initial experimental validation of a computational design procedure aimed at generating enzyme-like protein catalysts called “protozymes” are reported, suggesting a possible mechanism for examining the relationships between protein fold and the evolvability of protein function. Expand
Conformation of amino acid side-chains in proteins.
Configurations that are rare for exposed residues are even rarer for buried residues, suggesting that, while the folded structure puts little strain on side-chain conformations, the side- chain positions with the lowest energy in the unfolded structure are chosen preferentially during folding. Expand