• fold
  • Generally scores below 0.20 corresponds to randomly chosen unrelated proteins whereas structures with a score higher than 0.5 assume roughly the same fold. (wikipedia.org)
  • A quantitative study shows that proteins of TM-score = 0.5 have a posterior probability of 37% in the same CATH topology family and of 13% in the same SCOP fold family. (wikipedia.org)
  • There are multiple fold classes of globular proteins, since there are many different architectures that can fold into a roughly spherical shape. (wikipedia.org)
  • The term globin can refer more specifically to proteins including the globin fold. (wikipedia.org)
  • Although it is still unknown how proteins fold up naturally, new evidence has helped advance understanding. (wikipedia.org)
  • Globular proteins seem to have two mechanisms for protein folding, either the diffusion-collision model or nucleation condensation model, although recent findings have shown globular proteins, such as PTP-BL PDZ2, that fold with characteristic features of both models. (wikipedia.org)
  • These new findings have shown that the transition states of proteins may affect the way they fold. (wikipedia.org)
  • Prions are infectious agents composed entirely of a protein material that can fold in multiple, structurally abstract ways, at least one of which is transmissible to other prion proteins, leading to disease in a manner that is epidemiologically comparable to the spread of viral infection. (wikipedia.org)
  • All known prions induce the formation of an amyloid fold, in which the protein polymerises into an aggregate consisting of tightly packed beta sheets. (wikipedia.org)
  • The millisecond regime for all-atom simulations was not reached until 2010, and it is still not possible to fold all real proteins on a computer. (wikipedia.org)
  • whereas
  • Enzymes called arginine deiminases (ADIs) catalyze the deimination of free arginine, while protein arginine deiminases or peptidylarginine deiminases (PADs) replace the primary ketimine group (=NH) by a ketone group (=O). Arginine is positively charged at a neutral pH, whereas citrulline has no net charge. (wikipedia.org)
  • The phosphorylated tyrosines are often used as "handles" by which proteins can bind to one another, whereas phosphorylation of Ser/Thr often induces conformational changes, presumably because of the introduced negative charge. (wikipedia.org)
  • conformation
  • A general paradigm for de novo prediction involves sampling conformation space, guided by scoring functions and other sequence-dependent biases such that a large set of candidate ("decoy") structures are generated. (wikipedia.org)
  • Globular proteins are only marginally stable because the free energy released when the protein folded into its native conformation is relatively small. (wikipedia.org)
  • Conformation analysis of proteins (PhD thesis). (wikipedia.org)
  • In particular, lattice models have been used to investigate the energy landscapes of proteins, i.e. the variation of their internal free energy as a function of conformation. (wikipedia.org)
  • sequence
  • At the beginning of 2008, only about 1% of the sequences listed in the UniProtKB database corresponded to structures in the Protein Data Bank (PDB), leaving a gap between sequence and structure of approximately five million. (wikipedia.org)
  • In light of experimental limitations, devising efficient computer programs to close the gap between known sequence and structure is believed to be the only feasible option. (wikipedia.org)
  • However, these preferences are not strong enough to produce a reliable method of predicting secondary structure from sequence alone. (wikipedia.org)
  • He has also worked on simplified representations of protein structure for analysing folding and packing, as well as developing scoring systems for large-scale sequence-structure comparisons. (wikipedia.org)
  • Francis Crick recognized the potential significance of the Griffith protein-only hypothesis for scrapie propagation in the second edition of his "Central dogma of molecular biology" (1970): While asserting that the flow of sequence information from protein to protein, or from protein to RNA and DNA was "precluded", he noted that Griffith's hypothesis was a potential contradiction (although it was not so promoted by Griffith). (wikipedia.org)
  • For any sequence in any particular structure, an energy can be rapidly calculated from the energy function. (wikipedia.org)
  • Most researchers consider a lattice protein sequence protein-like only if it possesses a single structure with an energetic state lower than in any other structure. (wikipedia.org)
  • By varying the energy function and the bead sequence of the chain (the primary structure), effects on the native state structure and the kinetics of folding can be explored, and this may provide insights into the folding of real proteins. (wikipedia.org)
  • Protein primary structure is the linear sequence of amino acids in a peptide or protein. (wikipedia.org)
  • Protein sequence is typically notated as a string of letters, listing the amino acids starting at the amino-terminal end through to the carboxyl-terminal end. (wikipedia.org)
  • Large sequence databases now exist that collate known protein sequences. (wikipedia.org)
  • synthesis
  • Chemical methods typically synthesise peptides in the opposite order to biological protein synthesis (starting at the C-terminus). (wikipedia.org)
  • hypothesis
  • The science of the tertiary structure of proteins has progressed from one of hypothesis to one of detailed definition. (wikipedia.org)
  • During the 1960s, two London-based researchers, radiation biologist Tikvah Alper and biophysicist John Stanley Griffith, developed the hypothesis that some transmissible spongiform encephalopathies are caused by an infectious agent consisting solely of proteins. (wikipedia.org)
  • biological
  • Since the vision is of a large collection of atoms with subgroupings of atoms that work together in a complex dynamic manner, a protein would be a collection of atoms, many of which are covalently bonded, that interact together to perform a specific biological function. (wikipedia.org)
  • Samudrala's work has thus focussed on proteins, which is the fundamental unit of biological function within the structeome. (wikipedia.org)
  • In biological systems, proteins are produced during translation by a cell's ribosomes. (wikipedia.org)
  • typically
  • Typically, protein samples above 97% purity are considered suitable for crystallization[citation needed], although high purity is neither necessary nor sufficient for crystallization. (wikipedia.org)
  • Different versions of lattice proteins may adopt different types of lattice (typically square and triangular ones), in two or three dimensions, but it has been shown that generic lattices can be used and handled via a uniform approach. (wikipedia.org)
  • side chains
  • Finally, the peptide side chains can also be modified covalently, e.g., phosphorylation Aside from cleavage, phosphorylation is perhaps the most important chemical modification of proteins. (wikipedia.org)
  • notably
  • The supramolecular association of β-sheets has been implicated in formation of the protein aggregates and fibrils observed in many human diseases, notably the amyloidoses such as Alzheimer's disease. (wikipedia.org)
  • While some protein crystals have been observed in nature, protein crystallization is predominantly used for scientific or industrial purposes, most notably for study by X-ray crystallography. (wikipedia.org)
  • often
  • Other extended structures such as the polyproline helix and alpha sheet are rare in native state proteins but are often hypothesized as important protein folding intermediates. (wikipedia.org)
  • The TM-score is intended as a more accurate measure of the quality of full-length protein structures than the often used RMSD and GDT measures. (wikipedia.org)
  • Determination of appropriate crystallization conditions for a given protein often requires empirical testing of many conditions before a successful crystallization condition is found. (wikipedia.org)
  • In rheumatoid arthritis and other autoimmune diseases, such as psoriatic arthritis, systemic lupus erythematosus and Sjögren's syndrome, autoantibodies often attack citrullinated proteins. (wikipedia.org)
  • The research showed that remotely related proteins identified by threading often share a common ligand binding site occupied by chemically similar ligands that contain strongly conserved anchor functional groups as well as a variable region that accounts for their binding specificity. (wikipedia.org)
  • One notable use was detecting many millions of errors (often small, but sometimes catastrophic) in Protein Data Bank (PDB) files. (wikipedia.org)
  • bind
  • The folding of globular proteins has also recently been connected to treatment of diseases, and anti-cancer ligands have been developed which bind to the folded but not the natural protein. (wikipedia.org)
  • The thiol group also has a high affinity for heavy metals, so that proteins containing cysteine, such as metallothionein, will bind metals such as mercury, lead and cadmium tightly. (wikipedia.org)
  • computational
  • In 2010, he again became a finalist and went on to receive the Pioneer Award for his Computational Analysis of Novel Drug Opportunities (CANDO) drug discovery platform to screen every known drug against every known target structure in a shotgun manner to discover new repurposeable therapeutics, particularly for underserved diseases. (wikipedia.org)
  • Because proteins are such large molecules, there are severe computational limits on the simulated timescales of their behaviour when modeled in all-atom detail. (wikipedia.org)
  • Simplifications of this kind significantly reduce the computational effort in handling the model, although even in this simplified scenario the protein folding problem is NP-complete. (wikipedia.org)
  • citation needed
  • citation needed] In 1982, Stanley B. Prusiner of the University of California, San Francisco announced that his team had purified the hypothetical infectious prion, and that the infectious agent consisted mainly of a specific protein - though they did not manage to isolate the protein until two years after Prusiner's announcement. (wikipedia.org)
  • large
  • Proteins have irregularly shaped surfaces, which results in the formation of large channels within any protein crystal. (wikipedia.org)
  • Skolnick is most known for demonstrating that the number of ligand binding pockets in proteins is quite small, thereby justifying the likelihood that large scale drug repurposing will work. (wikipedia.org)
  • experimental
  • Experimental techniques for determining tertiary structure have faced serious bottlenecks in their ability to determine structures for particular proteins. (wikipedia.org)
  • Most protein crystallization techniques form crystals by salting out the protein into crystals, although some experimental setups can produce crystals using the salting in effect. (wikipedia.org)
  • This combined with the ability to use predicted as well as experimental structures in virtual ligand screening at higher accuracy and precision than existing approaches will enable FDA approved drugs with novel mechanisms of action to be identified computationally with a high likelihood of experimental success. (wikipedia.org)
  • These insights enable low-resolution predicted structures to be used for ligand screening/binding pose prediction, with comparable accuracy as with high-resolution experimental structures. (wikipedia.org)
  • In virtual ligand screening, the latest version, FINDSITEcomb, was shown to work far better than more traditional virtual screening approaches on both predicted and high resolution experimental structures. (wikipedia.org)
  • crystallography
  • Prior to Bernal and Hodgkin, protein crystallography had only been performed in dry conditions with inconsistent and unreliable results. (wikipedia.org)
  • In 1958, the structure of myoglobin, determined by X-ray crystallography, was first reported by John Kendrew. (wikipedia.org)
  • molecules
  • Like many other types of molecules, proteins can be prompted to form crystals when the solution in which they are dissolved becomes supersaturated. (wikipedia.org)
  • Crystallization of protein molecules has been known for over 150 years. (wikipedia.org)
  • The solubility of protein molecules is subject to many factors, especially the interaction with other compounds in solution. (wikipedia.org)
  • displaystyle
  • The TM-score indicates the difference between two structures by a score between ( 0 , 1 ] {\displaystyle (0, , where 1 indicates a perfect match between two structures (thus the higher the better). (wikipedia.org)