Biomaterial Database

Cooperativity in protein folding: from lattice models with sidechains to real proteins. 1998

D K Klimov, and D Thirumalai

Institute for Physical Science and Technology, University of Maryland, College Park 20742, USA. klimov@glue.umd.edu

BACKGROUND Over the past few years novel folding mechanisms of globular proteins have been proposed using minimal lattice and off-lattice models. The factors determining the cooperativity of folding in these models and especially their explicit relation to experiments have not been fully established, however. RESULTS We consider equilibrium folding transitions in lattice models with and without sidechains. A dimensionless measure, omega c, is introduced to quantitatively assess the degree of cooperativity in lattice models and in real proteins. We show that larger values of omega c resembling the values seen in proteins are obtained in lattice models with sidechains. The enhanced cooperativity of such models results from possible denser packing of sidechains in the interior of the model polypeptide chain. We also establish that omega c correlates extremely well with sigma T = (T o - T f) /T o, where T o and T f are collapse and folding transition temperatures, respectively. These theoretical ideas are used to analyze folding transitions in two-state folders (RNase A, chymotrypsin inhibitor 2, fibronectin type III modules and tendamistat) and three-state folders (apomyoglobin and lysozyme). The values of omega c extracted from experiments show a correlation with sigma T (suitably generalized when folding is induced by denaturants or acid). CONCLUSIONS A quantitative description of the cooperative transition of real proteins can be made by lattice models with sidechains. The degree of cooperativity in minimal models and real proteins can be expressed in terms of the single parameter sigma, which can be estimated from experimental data.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D010455	Peptides	Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.	Peptide,Polypeptide,Polypeptides
D010940	Plant Proteins	Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which PLANT PROTEINS, DIETARY is available.	Plant Protein,Protein, Plant,Proteins, Plant
D011489	Protein Denaturation	Disruption of the non-covalent bonds and/or disulfide bonds responsible for maintaining the three-dimensional shape and activity of the native protein.	Denaturation, Protein,Denaturations, Protein,Protein Denaturations
D011506	Proteins	Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.	Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D005353	Fibronectins	Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.	Cold-Insoluble Globulins,LETS Proteins,Fibronectin,Opsonic Glycoprotein,Opsonic alpha(2)SB Glycoprotein,alpha 2-Surface Binding Glycoprotein,Cold Insoluble Globulins,Globulins, Cold-Insoluble,Glycoprotein, Opsonic,Proteins, LETS,alpha 2 Surface Binding Glycoprotein
D006863	Hydrogen-Ion Concentration	The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH	pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D012260	Ribonucleases	Enzymes that catalyze the hydrolysis of ester bonds within RNA. EC 3.1.-.	Nucleases, RNA,RNase,Acid Ribonuclease,Alkaline Ribonuclease,Ribonuclease,RNA Nucleases,Ribonuclease, Acid,Ribonuclease, Alkaline
D013696	Temperature	The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.	Temperatures
D013816	Thermodynamics	A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)	Thermodynamic