T e purpose of this review is to assess the nature and magnitudes of the dominant forces in protein folding. Since proteins are only marginally stable at room temperature,’ no type of molecular interaction is unimportant, and even small interactions can contribute significantly (positively or negatively) to stability (Alber, 1989a,b; Matthews, 1987a,b). However, the present review aims to identify only the largest forces that lead to the structural features of globular proteins: their extraordinary compactness, their core of nonpolar residues, and their considerable amounts of internal architecture. This review explores contributions to the free energy of folding arising from electrostatics (classical charge repulsions and ion pairing), hydrogen-bonding and van der Waals interactions, intrinsic propensities, and hydrophobic interactions. An earlier review by Kauzmann (1959) introduced the importance of hydrophobic interactions. His insights were particularly remarkable considering that he did not have the benefit of known protein structures, model studies, high-resolution calorimetry, mutational methods, or force-field or statistical mechanical results. The present review aims to provide a reassessment of the factors important for folding in light of current knowledge. Also considered here are the opposing forces, conformational entropy and electrostatics. The process of protein folding has been known for about 60 years. In 1902, Emil Fischer and Franz Hofmeister independently concluded that proteins were chains of covalently linked amino acids (Haschemeyer & Haschemeyer, 1973) but deeper understanding of protein structure and conformational change was hindered because of the difficulty in finding conditions for solubilization. Chick and Martin (191 1) were the first to discover the process of denaturation and to distinguish it from the process of aggregation. By 1925, the denaturation process was considered to be either hydrolysis of the peptide bond (Wu & Wu, 1925; Anson & Mirsky, 1925) or dehydration of the protein (Robertson, 1918). The view that protein denaturation was an unfolding process was

/pdf/dominant-forces-in-protein-folding-42bjzlldw4.pdf

Dominant forces in protein folding

Starting from known properties of non-specific salt effects on the surface tension at an air–water interface, we propose the first general, detailed qualitative molecular mechanism for the origins of ion-specific (Hofmeister) effects on the surface potential difference at an air–water interface; this mechanism suggests a simple model for the behaviour of water at all interfaces (including water–solute interfaces), regardless of whether the non-aqueous component is neutral or charged, polar or non-polar Specifically, water near an isolated interface is conceptually divided into three layers, each layer being 1 water-molecule thick We propose that the solute determines the behaviour of the adjacent first interfacial water layer ( I 1 ); that the bulk solution determines the behaviour of the third interfacial water layer ( I 3 ), and that both I 1 and I 3 compete for hydrogen-bonding interactions with the intervening water layer ( I 2 ), which can be thought of as a transition layer The model requires that a polar kosmotrope (polar water-structure maker) interact with I 1 more strongly than would bulk water in its place; that a chaotrope (water-structure breaker) interact with I 1 somewhat less strongly than would bulk water in its place; and that a non-polar kosmotrope (non-polar water-structure maker) interact with I 1 much less strongly than would bulk water in its place We introduce two simple new postulates to describe the behaviour of I 1 water molecules in aqueous solution The first, the ‘relative competition’ postulate, states that an I 1 water molecule, in maximizing its free energy (—δG), will favour those of its highly directional polar (hydrogen-bonding) interactions with its immediate neighbours for which the maximum pairwise enthalpy of interaction (—δ H ) is greatest; that is, it will favour the strongest interactions We describe such behaviour as ‘compliant’, since an I 1 water molecule will continually adjust its position to maximize these strong interactions Its behaviour towards its remaining immediate neighbours, with whom it interacts relatively weakly (but still favourably), we describe as ‘recalcitrant’, since it will be unable to adjust its position to maximize simultaneously these interactions The second, the ‘charge transfer’ postulate, states that the strong polar kosmotrope–water interaction has at least a small amount of covalent character, resulting in significant transfer of charge from polar kosmotropes to water–especially of negative charge from Lewis bases (both neutral and anionic); and that the water-structuring effect of polar kosmotropes is caused not only by the tight binding (partial immobilization) of the immediately adjacent ( I 1 ) water molecules, but also by an attempt to distribute among several water molecules the charge transferred from the solute When extensive, cumulative charge transfer to solvent occurs, as with macromolecular polyphosphates, the solvation layer (the layer of solvent whose behaviour is determined by the solute) can become up to 5- or 6-water-molecules thick We then use the ‘relative competition’ postulate, which lends itself to simple diagramming, in conjunction with the ‘charge transfer’ postulate to provide a new, startlingly simple and direct qualitative explanation for the heat of dilution of neutral polar solutes and the temperature dependence of relative viscosity of neutral polar solutes in aqueous solution This explanation also requires the new and intriguing general conclusion that as the temperature of aqueous solutions is lowered towards o °C, solutes tend to acquire a non-uniform distribution in the solution, becoming increasingly likely to cluster 2 water molecules away from other solutes and surfaces (the driving force for this process being the conversion of transition layer water to bulk water) The implications of these conclusions for understanding the mechanism of action of general (gaseous) anaesthetics and other important interfacial phenomena are then addressed

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0033583500005369

The Hofmeister effect and the behaviour of water at interfaces.

Publisher Summary This chapter focuses on the stability of protein structure and hydrophobic interaction The interest in hydrophobic interactions was stimulated by their unusual thermodynamic properties: it is believed that they are governed, not by enthalpic, but by entropic features, characterized by the undesirable entropy decrease of water in the vicinity of nonpolar groups The amount of polar groups in proteins is almost the same as the amount of nonpolar ones; and according to crystallographic studies, most of them are arranged at distances suggesting hydrogen bond formation Hydrogen bonds were invoked to various degrees of importance in explaining the stabilization of the native structure The chapter examines the main achievements of microcalorimetric studies of protein denaturation and of the dissolution of nonpolar substances in water The chapter also discusses calorimetric studies of protein denaturation The denaturational increment of the heat capacity can be partly explained by a gradual melting of the residual structure in the denatured protein on heating The large negative entropy of the transfer of a nonpolar substance to water at room temperature indicates a definite increase of the order in water in the presence of such solutes Of the two approaches to decomposing the thermodynamics for dissolution of nonpolar solutes into water, the first, from a reference point at the maximum of the free energy of transfer, leads to the concept of the compact state of the nonpolar substance

Stability of protein structure and hydrophobic interaction.

Calculation of the thermodynamic and transport properties of aqueous species at high pressures and temperatures: Standard partial molal properties of organic species

The Schizophrenia Patient Outcomes Research Team (PORT) psychosocial treatment recommendations provide a comprehensive summary of current evidence-based psychosocial treatment interventions for persons with schizophrenia. There have been 2 previous sets of psychosocial treatment recommendations (Lehman AF, Steinwachs DM. Translating research into practice: the Schizophrenia Patient Outcomes Research Team (PORT) treatment recommendations. Schizophr Bull. 1998;24:1-10 and Lehman AF, Kreyenbuhl J, Buchanan RW, et al. The Schizophrenia Patient Outcomes Research Team (PORT): updated treatment recommendations 2003. Schizophr Bull. 2004;30:193-217). This article reports the third set of PORT recommendations that includes updated reviews in 7 areas as well as adding 5 new areas of review. Members of the psychosocial Evidence Review Group conducted reviews of the literature in each intervention area and drafted the recommendation or summary statement with supporting discussion. A Psychosocial Advisory Committee was consulted in all aspects of the review, and an expert panel commented on draft recommendations and summary statements. Our review process produced 8 treatment recommendations in the following areas: assertive community treatment, supported employment, cognitive behavioral therapy, family-based services, token economy, skills training, psychosocial interventions for alcohol and substance use disorders, and psychosocial interventions for weight management. Reviews of treatments focused on medication adherence, cognitive remediation, psychosocial treatments for recent onset schizophrenia, and peer support and peer-delivered services indicated that none of these treatment areas yet have enough evidence to merit a treatment recommendation, though each is an emerging area of interest. This update of PORT psychosocial treatment recommendations underscores both the expansion of knowledge regarding psychosocial treatments for persons with schizophrenia at the same time as the limitations in their implementation in clinical practice settings.

/pdf/the-2009-schizophrenia-port-psychosocial-treatment-1fjw29af6n.pdf

The 2009 Schizophrenia PORT Psychosocial Treatment Recommendations and Summary Statements

Volume Changes in Hydrocarbon—Water Systems. Partial Molal Volumes of Alcohol—Water Solutions1

Structural studies of ribonuclease. XXII. Location of the third buried tyrosyl residue in ribonuclease.

Structural Studies of Ribonuclease. XXVI. The Role of Tyrosine 115 in the Refolding of Ribonuclease

Iodination of ribonuclease in the presence of cytidine 3′-phosphate

Metabolism of uniformly labeled [14C] maltotriose in the rat

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Michael E. Friedman

Author Tools

Chat about Author