المؤلفون: Hue Sun Chan, Sarina Bromberg, Paul Thomas, David P. Yee, Ken A. Dill, Klaus M. Fiebig, Kaizhi Yue

المصدر: Protein Science. 4:561-602

مصطلحات موضوعية: Models, Molecular, Protein Denaturation, Protein Folding, Protein Conformation, Chemistry, Molecular Sequence Data, Temperature, Hydrogen Bonding, Cooperativity, Biological Evolution, Biochemistry, Levinthal's paradox, Hydrophobic effect, Crystallography, Protein structure, Chemical physics, Mutation, Lattice protein, Thermodynamics, Protein folding, Amino Acid Sequence, Hydrophobic collapse, Molecular Biology, Native contact, Research Article

الوصف: General principles of protein structure, stability, and folding kinetics have recently been explored in computer simulations of simple exact lattice models. These models represent protein chains at a rudimentary level, but they involve few parameters, approximations, or implicit biases, and they allow complete explorations of conformational and sequence spaces. Such simulations have resulted in testable predictions that are sometimes unanticipated: The folding code is mainly binary and delocalized throughout the amino acid sequence. The secondary and tertiary structures of a protein are specified mainly by the sequence of polar and nonpolar monomers. More specific interactions may refine the structure, rather than dominate the folding code. Simple exact models can account for the properties that characterize protein folding: two-state cooperativity, secondary and tertiary structures, and multistage folding kinetics--fast hydrophobic collapse followed by slower annealing. These studies suggest the possibility of creating "foldable" chain molecules other than proteins. The encoding of a unique compact chain conformation may not require amino acids; it may require only the ability to synthesize specific monomer sequences in which at least one monomer type is solvent-averse.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::95a3de7f24e0135dee51662a22123277Test
https://doi.org/10.1002/pro.5560040401Test

المؤلفون: Ken A. Dill, Kaizhi Yue, Kohki Ishikawa

المصدر: Protein Science. 8:716-721

مصطلحات موضوعية: Models, Molecular, chemistry.chemical_classification, Quantitative Biology::Biomolecules, Protein Conformation, Chemistry, Protein design, Ab initio, Phi value analysis, Peptide, computer.file_format, Protein Data Bank, Biochemistry, Protein Structure, Secondary, Kinetics, Crystallography, Protein structure, Molecular Biology, computer, Statistical potential, Peptide sequence, Algorithms, Software, Research Article

الوصف: We describe an extensive test of Geocore, an ab initio peptide folding algorithm. We studied 18 short molecules for which there are structures in the Protein Data Bank; chains are up to 31 monomers long. Except for the very shortest peptides, an extremely simple energy function is sufficient to discriminate the true native state from more than 10(8) lowest energy conformations that are searched explicitly for each peptide. A high incidence of native-like structures is found within the best few hundred conformations generated by Geocore for each amino acid sequence. Predictions improve when the number of discrete phi/psi choices is increased.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e1da907349615becf6a0b56c87fb0433Test
https://doi.org/10.1110/ps.8.4.716Test

المؤلفون: Kaizhi Yue, Ken A. Dill

المصدر: Protein Science. 5:254-261

مصطلحات موضوعية: chemistry.chemical_classification, Globular protein, Computational biology, Biochemistry, Melittin, Amino acid, Folding (chemistry), chemistry.chemical_compound, Protein structure, chemistry, Computational chemistry, Lattice protein, Protein folding, Molecular Biology, Peptide sequence

الوصف: We describe a computer algorithm for predicting the three-dimensional structures of proteins using only their amino acid sequences. The method differs from others in two ways: (1) it uses very few energy parameters, representing hydrophobic and polar interactions, and (2) it uses a new “constraint-based exhaustive” searching method, which appears to be among the fastest and most complete search methods yet available for realistic protein models. It finds a relatively small number of low-energy conformations, among which are native-like conformations, for cram-bin (1CRN), avian pancreatic polypeptide (1PPT), melittin (2MLT), and apamin. Thus, the lowest-energy states of very simple energy functions may predict the native structures of globular proteins.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::c174d8c031ab024c9b033e57af41f1ddTest
https://doi.org/10.1002/pro.5560050209Test

المؤلفون: Kaizhi Yue, Ken A. Dill

المصدر: Proceedings of the National Academy of Sciences. 89:4163-4167

مصطلحات موضوعية: Quantitative Biology::Biomolecules, Sequence, Multidisciplinary, Chemistry, Proteins, Hydrogen Bonding, Topology, Folding (chemistry), Structure-Activity Relationship, Crystallography, Solubility, Drug Design, Lattice protein, Helix, Native state, Protein folding, Folding funnel, Lattice model (physics), Research Article

الوصف: We consider the question of how to design proteins. How can we find "good" amino acid sequences (i) that fold to a desired "target" structure as a native conformation of lowest accessible free energy and (ii) that will not simultaneously fold to many other conformations of the same free energy? Current protein designs often focus on helix propensities and turns. We focus here on designing the hydrophobicity. For a model of self-avoiding hydrophobic/polar chains on two-dimensional square lattices, geometric proofs and exhaustive enumerations show the following results. (i) The strategy hydrophobic residues inside/polar residues outside is not optimal. Placement of additional hydrophobic residues on the surface is often necessary. (ii) To avoid unwanted conformations, the designed sequence must have neither too many nor too few hydrophobic residues. (iii) The computational complexity of inverse folding appears to be in a different class than folding: unlike the folding problem, the design problem does not scale exponentially with chain length. Some design strategies, described here for the lattice model, produce good sequences and scale only linearly with chain length.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1f2c2857c1b824e4a44e288743160906Test
https://doi.org/10.1073/pnas.89.9.4163Test

المؤلفون: Kaizhi Yue, Ken A. Dill

المصدر: Proceedings of the National Academy of Sciences of the United States of America. 92(1)

مصطلحات موضوعية: chemistry.chemical_classification, Models, Molecular, Quantitative Biology::Biomolecules, Multidisciplinary, Globular protein, Molecular Sequence Data, Proteins, Sequence (biology), Biology, Models, Theoretical, Protein Structure, Secondary, Protein Structure, Tertiary, Crystallography, Orders of magnitude (time), chemistry, Simple (abstract algebra), Homogeneous space, Polar, Degeneracy (biology), Computer Simulation, Statistical physics, Amino Acid Sequence, Peptide sequence, Research Article

الوصف: The tertiary structures of globular proteins have remarkable and complex symmetries. What forces cause them? We find that a very simple model reproduces some of those symmetries. Proteins are modeled as copolymers of specific sequences of hydrophobic (H) and polar (P) monomers (HP model) configured as self-avoiding flights on simple three-dimensional cubic lattices. The model has no parameters; we just seek the conformations that have the global maximum number of HH contacts for any given sequence. Finding global optima for chains in this model has not been computationally possible before for chains longer than 36-mers. We report here a procedure that can find all the globally optimal conformations, the number of which defines the degeneracy of a sequence, for chains up to 88 monomers long. It is about 37 orders of magnitude faster than previous exact methods. We find that degeneracy is an important aspect of sequence design. So far, we have found that four-helix bundles, alpha/beta-barrels, and parallel beta-helices are globally optimal conformations of polar/nonpolar sequences that have minimal degeneracy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8b2329f09aff43ce8e0aadb1b2b791d2Test
https://pubmed.ncbi.nlm.nih.gov/7816806Test

المؤلفون: Ken A. Dill, Kaizhi Yue

المصدر: Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics. 48(3)

مصطلحات موضوعية: Combinatorics, Quantitative Biology::Biomolecules, chemistry.chemical_compound, Monomer, Speedup, chemistry, Lattice (order), Native state, Copolymer, Polar, Sequence structure, Upper and lower bounds, Mathematics

الوصف: We model proteins as copolymer chains of H (hydrophobic) and P (polar) monomers configured as self-avoiding flights on three-dimensional simple-cubic lattices. The HH interaction is favorable. The folding problem is to find the ``native'' conformation(s) (lowest free energy) for an HP sequence. Using geometric proofs for self-avoiding lattice chains, we develop equations relating a monomer sequence to its native structures. These constraint relations can be used for two purposes: (1) to compute a tight lower bound on the free energy of the native state for HP sequences of any length, which is useful for testing conformational search strategies, and (2) to develop a search strategy. In its present implementation, the search strategy finds native states for HP lattice chains up to 36 monomers in length, which is a speedup of 5\char21{}15 orders of magnitude over existing brute-force exhaustive-search methods.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9ed2fb4a376cdd9b522d7a1548f37ffbTest
https://pubmed.ncbi.nlm.nih.gov/9960847Test