Inverse Protein Folding in 3D Hexagonal Prism Lattice under HP Model (original) (raw)
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Inverse Protein Folding in 3D Hexagonal Prism Lattice under HPC Model
Journal of Computational Biology, 2009
The inverse protein folding problem is that of designing an amino acid sequence which has a prescribed native protein fold. This problem arises in drug design where a particular structure is necessary to ensure proper protein-protein interactions. In , a tubular structures for 3D hexagonal prism lattice were introduced and their stability was formally proved for simple instances under the HP model of Dill. In this paper, we generalize the design of tubular structures to allow for much larger variety of designable structures by allowing branching of tubes. Our generalized design could be used to approximate given 3D shapes in the considered lattice. Although the generalized tubular structures are not stable under the HP model we can prove that a simple instance of generalized tubular structures is structurally stable (all native folds have the designed shape) under a refined version of HP model, called HPC model. We conjecture that all generalized tubular structures are structurally stable under the HPC model. * These authors contributed equally.
Stability of preferable structures for a hydrophobic-polar model of protein folding
Physical Review E, 1998
By exact computer enumeration we have calculated the designability of proteins in a simple lattice hydrophobic-polar model for the protein folding problem. We show that if the strength of the nonadditive part of the interaction potential becomes larger than a critical value, the degree of designability of structures will depend on the parameters of potential.
Shape-dependent designability studies of lattice proteins
Journal of Physics: Condensed Matter, 2007
One important problem in computational structural biology is protein designability, that is, why protein sequences are not random strings of amino acids but instead show regular patterns that encode protein structures. Many previous studies that have attempted to solve the problem have relied upon reduced models of proteins. In particular, the 2D square and the 3D cubic lattices together with reduced amino acid alphabet models have been examined extensively and have lead to interesting results that shed some light on evolutionary relationship among proteins. Here we perform designability studies on the 2D square lattice and explore the effects of variable overall shapes on protein designability using a binary hydrophobic-polar (HP) amino acid alphabet. Because we rely on a simple energy function that counts the total number of H-H interactions between non-sequential residues, we restrict our studies to protein shapes that have the same number of residues and also a constant number of non-bonded contacts. We have found that there is a marked difference in the designability between various protein shapes, with some of them accounting for a significantly larger share of the total foldable sequences.
Physical Review E, 2001
We show that a nonspecific hydrophobic energy function can produce proteinlike folding behavior of a three-dimensional protein model of 40 monomers in the cubic lattice when the native conformation is chosen judiciously. We confirm that monomer inside/outside segregation is a powerful criterion for the selection of appropriate structures, an idea that was recently proposed with basis on a general theoretical analysis and simulations of much simpler two-dimensional models.
Designability of protein structures: A lattice-model study using the Miyazawa-Jernigan matrix
Proteins: Structure, Function, and Genetics, 2002
We study the designability of all compact 3×3×3 and 6×6 lattice-protein structures using the Miyazawa-Jernigan (MJ) matrix. The designability of a structure is the number of sequences that design the structure, i.e. sequences that have that structure as their unique lowest-energy state. Previous studies of hydrophobic-polar (HP) models showed a wide distribution of structure designabilities. Recently, questions were raised concerning the use of a 2-letter (HP) code in such studies. Here we calculate designabilities using all 20 amino acids, with empirically determined interaction potentials (MJ matrix), and compare with HP model results. We find good qualitative agreement between the two models. In particular, highly designable structures in the HP model are also highly designable in the MJ model-and vice versa-with the associated sequences having enhanced thermodynamic stability.
Principles for designing ideal protein structures
Unlike random heteropolymers, natural proteins fold into unique ordered structures. Understanding how these are encoded in amino-acid sequences is complicated by energetically unfavourable non-ideal features—for example kinked α-helices, bulged β-strands, strained loops and buried polar groups—that arise in proteins from evolutionary selection for biological function or from neutral drift. Here we describe an approach to designing ideal protein structures stabilized by completely consistent local and non-local interactions. The approach is 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. Guided by these rules, we designed sequences predicted to fold into ideal protein structures consisting of α-helices, β-strands and minimal loops. Designs for five different topologies were found to be monomeric and very stable and to adopt structures in solution nearly identical to the computational models. These results illuminate how the folding funnels of natural proteins arise and provide the foundation for engineering a new generation of functional proteins free from natural evolution.
Protein Design in a Lattice Model of Hydrophobic and Polar Amino Acids
Physical Review Letters, 1998
A general strategy is described for finding which amino acid sequences have native states in a desired conformation (inverse design). The approach is used to design sequences of 48 hydrophobic and polar aminoacids on threedimensional lattice structures. Previous studies employing a sequence-space Monte-Carlo technique resulted in the successful design of one sequence in ten attempts. The present work also entails the exploration of conformations that compete significantly with the target structure for being its ground state.
The Journal of Chemical Physics, 1993
Starting from amino acid sequence alone, a general approach for simulating folding into the molten globule or rigid, native state depending on sequence is described. In particular, the 3D folds of two simple designed proteins have been predicted using a Monte Carlo folding algorithm. The model employs a very flexible hybrid lattice representation of the protein conformation, and fast lattice dynamics. A full rotamer library for side group conformations, and potentials of mean force of short and long range interactions have been extracted from the statistics of a high resolution set of nonhomologous, 3D structures of globular proteins. The simulated folding process starts from an arbitrary random conformation and relatively rapidly assembles a well defined four helix bundle. The very cooperative folding of the model systems is facilitated by the proper definition of the model protein hydrogen bond network, and multibody interactions of the side groups. The two sequences studied exhibit very different behavior. The first one, in excellent agreement with experiment, folds to a thermodynamically very stable four helix bundle that has all the properties postulated for the molten globule state. The second protein, having a more heterogeneous sequence, at lower temperature undergoes a transition from the molten globule state to the unique native state exhibiting a fixed pattern of side group packing. This marks the first time that the ability to predict a molten globule or a unique native state from sequence alone has been achieved. The implications for the general solution of the protein folding problem are briefly discussed. 7420