Local rules for protein folding on a triangular lattice and generalized hydrophobicity in the HP model
Abstract
A long standing problem in molecular biology is to determine the threedimensional structure of a protein, given its amino acid sequence. A variety of simplifying models have been proposed abstracting only the {open_quotes}essential physical properties{close_quotes} of real proteins. In these models, the three dimensional space is often represented by a lattice. Residues which are adjacent in the primary sequence (i.e. covalently linked) must be placed at adjacent points in the lattice. A conformation of a protein is simply a selfavoiding walk along the lattice. The protein folding problem STRINGFOLD is that of finding a conformation of the protein sequence on the lattice such that the overall energy is minimized, for some reasonable definition of energy. This formulation leaves open the choices of a lattice and an energy function. Once these choices are made, one may then address the algorithmic complexity of optimizing the energy function for the lattice. For a variety of such simple models, this minimization problem is in fact NPhard. In this paper, we consider the HydrophobicPolar (HP) Model introduced by Dill. The HP model abstracts the problem by grouping the 20 amino acids into two classes: hydrophobic (or nonpolar) residues and hydrophilic (or polar) residues. For concreteness,more »
 Authors:
 National Institutes of Health, Bethesda, MD (United States)
 MIT Lab. for Computer Science, Cambridge, MA (United States)
 Univ. of Southern California, Los Angeles, CA (United States) [and others
 Publication Date:
 Research Org.:
 Association for Computing Machinery, New York, NY (United States); Sloan (Alfred P.) Foundation, New York, NY (United States)
 OSTI Identifier:
 548989
 Report Number(s):
 CONF970137
TRN: 97:0052980001
 Resource Type:
 Conference
 Resource Relation:
 Conference: RECOMB `97: 1. annual conference on research in computational molecular biology, Santa Fe, NM (United States), 2022 Jan 1997; Other Information: PBD: 1997; Related Information: Is Part Of RECOMB 97. Proceedings of the first annual international conference on computational molecular biology; PB: 370 p.
 Country of Publication:
 United States
 Language:
 English
 Subject:
 55 BIOLOGY AND MEDICINE, BASIC STUDIES; 99 MATHEMATICS, COMPUTERS, INFORMATION SCIENCE, MANAGEMENT, LAW, MISCELLANEOUS; PROTEINS; AMINO ACID SEQUENCE; PHYSICAL PROPERTIES; STRUCTUREACTIVITY RELATIONSHIPS; STRUCTURAL MODELS; ELECTRONIC STRUCTURE; TWODIMENSIONAL CALCULATIONS; THREEDIMENSIONAL CALCULATIONS; ALGORITHMS; S CODES; POLAR COMPOUNDS; COVALENCE; PROTEIN STRUCTURE; COMPUTERIZED SIMULATION; MOLECULAR BIOLOGY; ENERGY LEVELS
Citation Formats
Agarwala, R., Batzoglou, S., and Dancik, V.. Local rules for protein folding on a triangular lattice and generalized hydrophobicity in the HP model. United States: N. p., 1997.
Web.
Agarwala, R., Batzoglou, S., & Dancik, V.. Local rules for protein folding on a triangular lattice and generalized hydrophobicity in the HP model. United States.
Agarwala, R., Batzoglou, S., and Dancik, V.. 1997.
"Local rules for protein folding on a triangular lattice and generalized hydrophobicity in the HP model". United States.
doi:.
@article{osti_548989,
title = {Local rules for protein folding on a triangular lattice and generalized hydrophobicity in the HP model},
author = {Agarwala, R. and Batzoglou, S. and Dancik, V.},
abstractNote = {A long standing problem in molecular biology is to determine the threedimensional structure of a protein, given its amino acid sequence. A variety of simplifying models have been proposed abstracting only the {open_quotes}essential physical properties{close_quotes} of real proteins. In these models, the three dimensional space is often represented by a lattice. Residues which are adjacent in the primary sequence (i.e. covalently linked) must be placed at adjacent points in the lattice. A conformation of a protein is simply a selfavoiding walk along the lattice. The protein folding problem STRINGFOLD is that of finding a conformation of the protein sequence on the lattice such that the overall energy is minimized, for some reasonable definition of energy. This formulation leaves open the choices of a lattice and an energy function. Once these choices are made, one may then address the algorithmic complexity of optimizing the energy function for the lattice. For a variety of such simple models, this minimization problem is in fact NPhard. In this paper, we consider the HydrophobicPolar (HP) Model introduced by Dill. The HP model abstracts the problem by grouping the 20 amino acids into two classes: hydrophobic (or nonpolar) residues and hydrophilic (or polar) residues. For concreteness, we will take our input to be a string from (H,P){sup +}, where P represents polar residues, and H represents hydrophobic residues. Dill et.al. survey the literature analyzing this model. 8 refs., 2 figs., 1 tab.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = 1997,
month =
}

We consider the problem of determining the threedimensional folding of a protein given its onedimensional amino acid sequence. We use the HP model for protein folding proposed by Dill, which models protein as a chain of amino acid residues that are either hydrophobic or polar, and hydrophobic interactions are the dominant initial driving force for the protein folding. Hart and Istrail gave approximation algorithms for folding proteins on the cubic lattice under HP model. In this paper, we examine the choice of a lattice by considering its algorithmic and geometric implications and argue that triangular lattice is a more reasonablemore »

The earliest events in protein folding: Helix dynamics in proteins and model peptides
The earliest events in protein folding are critically important in determining the folding pathway, but have proved difficult to study by conventional approaches. We have developed new rapid initiation methods and structurespecific probes to interrogate the earliest events of protein folding. Our focus is the pathways. Folding or unfolding reactions are initiated on a fast timescale (10 ns) using a laser induced temperature jump (15 C) and probed with timeresolved infrared spectroscopy. We obtained the kinetics of the helixcoil transition for a model 21residue peptide. The observed rate constant k{sub obs} = k{sub f} + k{sub u} for reversible kinetics;more » 
Protein folding of the H0P model: A parallel WangLandau study
We propose a simple modication to the hydrophobicpolar (HP) protein model, by introducing a new type of monomer, "0", with intermediate hydrophobicity of some amino acids between H and P. With the replicaexchange WangLandau sampling method, we investigate some widely studied HP sequences as well as their H0P counterparts and observe that the H0P sequences exhibit dramatically reduced ground state degeneracy and more signicant transition signals at low temperature for some thermodynamic properties, such as the specific heat. 
Lattice and offlattice side chain models of protein folding: Linear time structure prediction better than 86% of optimal
This paper considers the protein structure prediction problem for lattice and offlattice protein folding models that explicitly represent side chains. Lattice models of proteins have proven extremely useful tools for reasoning about protein folding in unrestricted continuous space through analogy. This paper provides the first illustration of how rigorous algorithmic analyses of lattice models can lead to rigorous algorithmic analyses of offlattice models. The authors consider two side chain models: a lattice model that generalizes the HP model (Dill 85) to explicitly represent side chains on the cubic lattice, and a new offlattice model, the HP Tangent Spheres Side Chainmore »