DOCSLIB.ORG

Thermodynamics and Kinetics of Protein Incorporation Into Membranes

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Thermodynamics and Kinetics of Protein Incorporation Into Membranes Proc. NatL Acad. Sci. USA Vol. 80, pp. 3691-3695, June 1983 Biophysics Thermodynamics and kinetics of protein incorporation into membranes (hydrophobic effect/protein immobilization/lipid-protein interaction/hydrogen bonds/conformational entropy) FmRIZ JAHNIG Max-Planck-Institut fir Biologie, Corrensstrasse 38, 74 Tfibingen, Federal Republic of Germany Communicated by Hans Frauenfelder, February 9, 1983 ABSTRACT The free energy and enthalpy of protein incor- tein immobilization effect has not been taken into account in poration into membranes are calculated with special emphasis on previous work. This effect was studied in the context of en- the hitherto neglected effects of immobilization of protein and zyme-coenzyme binding where it was found to lead to a con- perturbation of lipid order in the membrane. The free energy siderable reduction of the binding energy available from the change is found to be determined by the hydrophobic effect as the hydrophobic effect (7, 8). The lipid perturbation effect also was driving force for incorporation and the protein immobilization ef- not considered previously, although a priori there is no reason fect which leads to a considerable reduction of the free energy for this contribution to be small because a large number of lipid gained from the hydrophobic effect. For incorporation of a hy- molecules may be affected by one protein molecule. From ca- drophobic, bilayer-spanning a-helix, the free energy change ob- lorimetric measurements it is known that enthalpies up to tained is of the order of -15 kcal/mol (1 cal = 4.184 J) in agree- hundreds of kcal/mol are involved in lipid-protein association ment with experimental results. The lipid perturbation effect yields (9-11). only a small contribution to the free energy change due to an en- of bind- ergy/entropy compensation inherent in lipid order. This effect In the present paper, the free energy and enthalpy dominates the enthalpy change, giving rise to values on the order ing of a protein to a membrane are calculated, including the of 100kcal/mol with a pronouncedtemperature dependence around hitherto neglected effects of protein immobilization and lipid the lipid phase transition as observed experimentally. The kinetics perturbation. The immobilization effect is estimated by a slight of protein incorporation are even more strongly affected by the modification of the treatment in enzyme-coenzyme binding lipid perturbation effect, leading to an abrupt decrease of the rate (8). The lipid perturbation effect is elaborated by adopting a of incorporation below the lipid phase transition. previously developed continuum model for lipid-protein in- teraction (12-14). The results for the free energy and enthalpy It is commonly accepted that the driving force for spontaneous of binding are compared with experimental data which have incorporation of proteins into membranes is the hydrophobic become available recently. The kinetics of protein incorpora- effect. However, a number of other effects may support or tion are discussed along similar lines by estimating the contri- counteract the hydrophobic effect. In general, the free energy butions of the individual effects to the activation free energy of protein incorporation includes four contributions which arise and enthalpy. from a change of (i) water structure, (ii) protein state, (iii) lipid state, and (iv) bonds between protein and water or lipid mol- Hydrophobic effect ecules. The change of water structure represents the hydrophobic The free energy gained from the hydrophobic effect upon in- effect which originates in the reduction of the mobility of water corporation of proteins into a lipid bilayer can be calculated in molecules surrounding the protein. The change of the protein two ways: (i) on the basis of the amino acid sequence and the state comprises the external translational and rotational degrees free energies of transfer of individual amino acid side chains of freedom which become immobilized upon incorporation of from water into the vapor phase (15) or into hydrocarbons (16); the protein and the internal degrees of freedom whose changes or (ii) from the change of the protein/water interfacial area and involve conformational changes and changes of internal bonds. a value for the free energy change per unit area (2). The second The change of the lipid state accounts for the reduction of the approach is used here. From studies of hydrocarbons and hy- mobility of the lipid molecules in a fluid membrane. This par- drophobic amino acids, the free energy per area was found to allels the reduction of the mobility of water molecules in the be 20-25 cal/(molFA2) (1 cal = 4.184 J) (2, 17). The interfacial hydrophobic effect and may therefore be called lipophobic ef- area is that area of a protein molecule that is accessible to water fect of proteins. The change of bonds at the protein surface molecules. It can be estimated by describing the protein as a concerns mainly polar interactions such as hydrogen bonds and sphere or cylinder and multiplying the corresponding smooth electrostatic interactions between polar amino acid residues and area by a factor of 1.7 to account for the unevenness of the pro- water molecules because the interaction energy between apolar tein surface (2). residues and water or lipid molecules is relatively small. Considering the simple case of a protein or protein segment The gain in free energy from the hydrophobic effect has been spanning the bilayer in the form of an a-helix, the helix is de- investigated thoroughly in the past (1-4). Estimates are also scribed as a cylinder of radius R.- 5 A and height h 30 A, available for the free energy arising from the formation or the thickness of the hydrophobic core of the bilayer. If the pro- breakage of hydrogen bonds and electrostatic bonds (3, 4) as tein also forms a helix in water, the change in effective inter- well as from the change of protein conformation (5, 6). The pro- facial area is 2irRoh1.7 1,600 A2. With a value of 22 cal/ (molA2) for the free energy per area, the free energy change The publication costs of this article were defrayed in part by page charge upon incorporation is AGw -35 kcal/mol of helix, as ob- payment. This article must therefore be hereby marked "advertise- tained by others (4). If the protein in water adopts an unfolded ment" in accordance with 18 U.S.C. §1734 solely to indicate this fact. conformation, the relevant area is that of a cylinder whose length 3691 Downloaded by guest on September 29, 2021 3692 Biophysics: jdhnig Proc. Natl. Acad. Sci. USA 80 (1983) is given by the number of amino acid residues, about 20, times mobilization is found to involve an energy change AGp 20 the length of one residue, 3.7 A, and whose radius is 3.2 A in kcal/mol. The concomitant enthalpy change AHp for the six order to yield the same volume as the a-helix. The change in degrees of freedom is -3RT or AHp- -2 kcal/mol. Hence, effective interfacial area then is 2,500 A2 leading to AGw = -55 the immobilization effect is also of predominantly entropic na- kcal/mol. ture like the hydrophobic effect. These values hold for com- Because the hydrophobic effect originates in the reduction plete immobilization of the protein in the membrane, which is of the mobility of water molecules, it is predominantly of en- not attained (at least not for a fluid membrane). One expects tropic nature. The enthalpy change is relatively small (1), less that only one translational and two rotational degrees of free- than a few kcal/mol, and, will be approximated by AHw 0. dom will be immobilized so that the above values for AGp and AHp are reduced by a factor of 1/2. Hydrogen bonds and conformational changes For this estimation, the immobilized degrees of freedom were treated simply as being lost. Actually, they are subject to the If hydrogen bonds between protein and water molecules are binding potential which still allows some relative motion. In a broken upon incorporation of the protein and not restored in more realistic approach one th ore may describe the im- the membrane, an energy of 5.8 kcal/mol of hydrogen bond mobilization of the translational degrees of freedom as the tran- is lost (18). To prevent this large loss of energy, protein mol- sition from a box of volume Vfree to a smaller one of volume ecules in the membrane adopt a conformation that allows the Vbound. The latter is given by the available membrane surface intramolecular formation of hydrogen bonds. This is optimal in area multiplied by a length 8z which measures the relative mo- an a-helical conformation. Hence, the hydrogen bonds are the tion between the incorporated protein and the membrane in cause for the frequently observed a-helical conformation of the direction of the membrane normal. The corresponding membrane-incorporated protein segments (4). This implies that change in free energy, assuming ideal gas behavior of the pro- hydrogen bonds do not contribute much to the free energy tein in the boxes, is AGt = NkT ln[Vfree/Vbound]. This immo- change of protein incorporation. bilization free energy is independent of the protein mass but Considering the final conformation of the protein in the depends on the lipid concentration. For a 0.1 mM lipid disc membrane as a-helical, the change in the internal degrees of persion, assuming a membrane surface area of 50 A2 per lipid freedom depends upon the protein conformation in water. If molecule and as an upper limit for the motion of the incor- the protein in water is also helical, the internal degrees of free- porated protein &z 1 A, one obtains AGt 8 kcal/mol.
Load more

Recommended publications
  • Heterogeneous Impacts of Protein-Stabilizing Osmolytes On
    bioRxiv preprint doi: https://doi.org/10.1101/328922; this version posted May 23, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Heterogeneous Impacts of Protein-Stabilizing Osmolytes on Hydrophobic Interaction Mrinmoy Mukherjee and Jagannath Mondal⇤ Tata Institute of Fundamental Research Hyderabad, 500107 India E-mail: [email protected],+914020203091 Abstract Osmolytes’ mechanism of protecting proteins against denaturation is a longstanding puzzle, further complicated by the complex diversities inherent in protein sequences. An emergent approach in understanding osmolytes’ mechanism of action towards biopoly- mer has been to investigate osmolytes’ interplay with hydrophobic interaction, the ma- jor driving force of protein folding. However, the crucial question is whether all these protein-stabilizing osmolytes display a single unified mechanism towards hydrophobic interactions. By simulating the hydrophobic collapse of a macromolecule in aqueous solutions of two such osmoprotectants, Glycine and Trimethyl N-oxide (TMAO), both of which are known to stabilize protein’s folded conformation, we here demonstrate that these two osmolytes can impart mutually contrasting effects towards hydropho- bic interaction. While TMAO preserves its protectant nature across diverse range of polymer-osmolyte interactions, glycine is found to display an interesting cross-over from being a protectant at weaker polymer-osmolyte interaction to a denaturant of hydrophobicity at stronger polymer-osmolyte interactions. A preferential-interaction analysis reveals that a subtle balance of conformation-dependent exclusion/binding of ⇤To whom correspondence should be addressed 1 bioRxiv preprint doi: https://doi.org/10.1101/328922; this version posted May 23, 2018.
    [Show full text]
  • Protein Structure & Folding
    6 Protein Structure & Folding To understand protein folding In the last chapter we learned that proteins are composed of amino acids Goal as a chemical equilibrium. linked together by peptide bonds. We also learned that the twenty amino acids display a wide range of chemical properties. In this chapter we will see Objectives that how a protein folds is determined by its amino acid sequence and that the three-dimensional shape of a folded protein determines its function by After this chapter, you should be able to: the way it positions these amino acids. Finally, we will see that proteins fold • describe the four levels of protein because doing so minimizes Gibbs free energy and that this minimization structure and the thermodynamic involves both making the most favorable bonds and maximizing disorder. forces that stabilize them. • explain how entropy (S) and enthalpy Proteins exhibit four levels of structure (H) contribute to Gibbs free energy. • use the equation ΔG = ΔH – TΔS The structure of proteins can be broken down into four levels of to determine the dependence of organization. The first is primary structure, the linear sequence of amino the favorability of a reaction on acids in the polypeptide chain. By convention, the primary sequence is temperature. written in order from the amino acid at the N-terminus (by convention • explain the hydrophobic effect and its usually on the left) to the amino acid at the C-terminus. The second level role in protein folding. of protein structure, secondary structure, is the local conformation adopted by stretches of contiguous amino acids.
    [Show full text]
  • Workshop 1 – Biochemistry (Chem 160)
    Workshop 1 – Biochemistry (Chem 160) 1. Draw the following peptide at pH = 7 and make sure to include the overall charge, label the N- and C-terminus, the peptide bond and the -carbon. AVDKY Give the overall charge of the peptide at pH = 3 and 12. 2. Draw a titration curve for Arg, make sure to label the different points. Determine the pI for Arg. 3. Nonpolar solute + water = solution a. What is the S of the universe, system and surroundings? The S of the universe would decrease this is why it is not spontaneous, the S of the system would increase but to a lesser extent to which the S of the surrounding would decrease S universe = S system + S surroundings 4. What is the hydrophobic effect and explain why it is thermodynamically favorable. The hydrophobic effect is when hydrophobic molecules tend to clump together burying them and placing hydrophilic molecules on the outside. The reason this is thermodynamically favorable is because it frees caged water molecules when burying clumping the hydrophobic molecules together. 5. Urea dissolves very readily in water, but the solution becomes very cold as the urea dissolves. How is this possible? Urea dissolves in water because when dissolving there is a net increase in entropy of the universe. The heat exchange, getting colder only reflects the enthalpy (H) component of the total energy change. The entropy change is high enough to offset the enthalpy component and to add up to an overall -G 6. A mutation that changes an alanine residue in the interior of a protein to valine is found to lead to a loss of activity.
    [Show full text]
  • Hydrophobic Effect, Water Structure, and Heat Capacity Changes
    J. Phys. Chem. B 1997, 101, 4343-4348 4343 Hydrophobic Effect, Water Structure, and Heat Capacity Changes Kim A. Sharp* and Bhupinder Madan Department of Biochemistry & Biophysics, UniVersity of PennsylVania, 3700 Hamilton Walk, Philadelphia, PennsylVania 19104-6059 ReceiVed: January 16, 1997; In Final Form: April 1, 1997X hyd The hydration heat capacity (∆Cp ) of nine solutes of varying hydrophobicity was studied using a combination of a random network model equation of water and Monte Carlo simulations. Nonpolar solutes cause a concerted decrease in the average length and angle of the water-water hydrogen bonds in the first hydration shell, while polar and ionic solutes have the opposite effect. This is due to changes in the amounts, relative to bulk water, of two populations of hydrogen bonds: one with shorter and more linear bonds and the other with longer and more bent bonds. Heat capacity changes were calculated from these changes in water structure using a random network model equation of state. The calculated changes account for observed hyd differences in ∆Cp for the various solutes. The simulations provide a unified picture of hydrophobic and hyd polar hydration, and both a structural and thermodynamic explanation of the opposite signs of ∆Cp observed for polar and nonpolar solutes. Introduction nonpolar groups means that at higher temperatures (T > 80 °C) their insolubility results from unfavorable changes in enthalpy, In recent years analysis of heat capacity changes has become not entropy. Second, the hydration of a majority of polar and of central importance in understanding the thermodynamics of ionic solutes is also accompanied by a decrease in entropy, and protein folding, protein-protein binding, protein-nucleic acid thus by some kind of structuring of water, but in this case binding, and the hydrophobic effect.1-7 There are several hyd 7,16-20 reasons for this.
    [Show full text]
  • Biological Membranes
    14 Biological Membranes To understand the structure The fundamental unit of life is the cell. All living things are composed of Goal and composition of biological cells, be it a single cell in the case of many microorganisms or a highly membranes. organized ensemble of myriad cell types in the case of multicellular organisms. A defining feature of the cell is a membrane, the cytoplasmic Objectives membrane, that surrounds the cell and separates the inside of the cell, the After this chapter, you should be able to cytoplasm, from other cells and the extracellular milieu. Membranes also • distinguish between cis and trans surround specialized compartments inside of cells known as organelles. unsaturated fatty acids. Whereas cells are typically several microns (μm) in diameter (although • explain why phospholipids some cells can be much larger), the membrane is only about 10 nanometers spontaneously form lipid bilayers and (nm) thick. Yet, and as we will see in subsequent chapters, the membrane is sealed compartments. not simply an ultra-thin, pliable sheet that encases the cytoplasm. Rather, • describe membrane fluidity and how it membranes are dynamic structures that mediate many functions in the is affected by membrane composition life of the cell. In this chapter we examine the composition of membranes, and temperature. their assembly, the forces that stabilize them, and the chemical and physical • explain the role of cholesterol in properties that influence their function. buffering membrane fluidity. The preceding chapters have focused on two kinds of biological molecules, • explain how the polar backbone namely proteins and nucleic acids, that are important in the workings of a membrane protein can be accommodated in a bilayer.
    [Show full text]
  • Hydrophobic Catalysis and a Potential Biological Role of DNA Unstacking Induced by Environment Effects
    Hydrophobic catalysis and a potential biological role of DNA unstacking induced by environment effects Bobo Fenga,1, Robert P. Sosab,c,d, Anna K. F. Mårtenssona, Kai Jiange, Alex Tongf, Kevin D. Dorfmang, Masayuki Takahashih, Per Lincolna, Carlos J. Bustamanteb,c,d,f,i,j,k,l, Fredrik Westerlunde, and Bengt Nordéna,1 aDepartment of Chemistry and Chemical Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden; bBiophysics Graduate Group, University of California, Berkeley, CA 94720; cJason L. Choy Laboratory of Single Molecule Biophysics, University of California, Berkeley, CA 94720; dInstitute for Quantitative Biosciences-QB3, University of California, Berkeley, CA 94720; eDepartment of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden; fDepartment of Chemistry, University of California, Berkeley, CA 94720; gDepartment of Chemical Engineering and Materials Science, University of Minnesota, Twin Cities, Minneapolis, MN 55455; hSchool of Life Science and Technology, Tokyo Institute of Technology, Tokyo 152-8550, Japan; iDepartment of Molecular & Cell Biology, University of California, Berkeley, CA 94720; jDepartment of Physics, University of California, Berkeley, CA 94720; kHoward Hughes Medical Institute, University of California, Berkeley, CA 94720; and lKavli Energy Nanosciences Institute, University of California, Berkeley, CA 94720 Edited by Feng Zhang, Broad Institute, Cambridge, MA, and approved July 22, 2019 (received for review May 27, 2019) Hydrophobic base stacking
    [Show full text]
  • Peptides & Proteins
    Peptides & Proteins (thanks to Hans Börner) 1 Proteins & Peptides Proteuos: Proteus (Gr. mythological figure who could change form) proteuo: „"first, ref. the basic constituents of all living cells” peptos: „Cooked referring to digestion” Proteins essential for: Structure, metabolism & cell functions 2 Bacterium Proteins (15 weight%) 50% (without water) • Construction materials Collagen Spider silk proteins 3 Proteins Structural proteins structural role & mechanical support "cell skeleton“: complex network of protein filaments. muscle contraction results from action of large protein assemblies Myosin und Myogen. Other organic material (hair and bone) are also based on proteins. Collagen is found in all multi cellular animals, occurring in almost every tissue. • It is the most abundant vertebrate protein • approximately a quarter of mammalian protein is collagen 4 Proteins Storage Various ions, small molecules and other metabolites are stored by complexation with proteins • hemoglobin stores oxygen (free O2 in the blood would be toxic) • iron is stored by ferritin Transport Proteins are involved in the transportation of particles ranging from electrons to macromolecules. • Iron is transported by transferrin • Oxygen via hemoglobin. • Some proteins form pores in cellular membranes through which ions pass; the transport of proteins themselves across membranes also depends on other proteins. Beside: Regulation, enzymes, defense, functional properties 5 Our universal container system: Albumines 6 zones: IA, IB, IIA, IIB, IIIA, IIIB; IIB and
    [Show full text]
  • Predicting Hydrophobic Alkyl-Alkyl and Perfluoroalkyl-Perfluoroalkyl Van
    Predicting hydrophobic alkyl-alkyl and perfluoroalkyl-perfluoroalkyl van der Waals dispersion interactions and their potential involvement in protein folding and the binding of drugs in hydrophobic pockets Clifford Fong To cite this version: Clifford Fong. Predicting hydrophobic alkyl-alkyl and perfluoroalkyl-perfluoroalkyl van der Waals dispersion interactions and their potential involvement in protein folding and the binding of drugs in hydrophobic pockets. [Research Report] Eigenenergy, Adelaide, Australia. 2019. hal-02176023v2 HAL Id: hal-02176023 https://hal.archives-ouvertes.fr/hal-02176023v2 Submitted on 5 Jan 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Predicting hydrophobic alkyl-alkyl and perfluoroalkyl-perfluoroalkyl van der Waals dispersion interactions and their potential involvement in protein folding and the binding of drugs in hydrophobic pockets Clifford W. Fong Eigenenergy, Adelaide, South Australia. Email: [email protected] Abstract It has been shown that a model compound which has previously allowed the experimental determination of the hydrophobic van der Waals dispersion alkyl-alkyl folding free energy interaction in a wide range of polar and non-polar solvents is strongly correlated with the cavitation, dispersion, solvent-structure (CDS) solvation free energy and to a lesser extent the molecular polarizability of the foldamers.
    [Show full text]
  • Probing the Base Stacking Contributions During
    PROBING THE BASE STACKING CONTRIBUTIONS DURING TRANSLESION DNA SYNTHESIS by BABHO DEVADOSS Submitted in partial fulfillment of the requirements For the degree of Doctor of Philosophy Thesis Adviser: Dr. Irene Lee Department of Chemistry CASE WESTERN RESERVE UNIVERSITY January, 2009 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of _____________________________________________________ candidate for the ______________________degree *. (signed)_______________________________________________ (chair of the committee) ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ (date) _______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. ii TABLE OF CONTENTS Title Page…………………………………………………………………………………..i Committee Sign-off Sheet………………………………………………………………...ii Table of Contents…………………………………………………………………………iii List of Tables…………………………………………………………………………….vii List of Figures…………………………………………………………………….………ix Acknowledgements…………………………………………………………….………..xiv List of Abbreviations…………………………………………………………….………xv Abstract………………………………………………………………………………….xix CHAPTER 1 Introduction…………………………………………………………………1 1.1 The Chemistry and Biology of DNA…………………………………………2 1.2 DNA Synthesis……………………………………………………………….6 1.3 Structural Features of DNA Polymerases…………………………………...11
    [Show full text]
  • The Hydrophobic Effect Oil and Water Do Not Mix. This Fact Is So Well
    The hydrophobic effect Oil and water do not mix. This fact is so well engrained in our ever-day experience that we never ask “why”. Well, today we are going to ask just this question: “why do oil and water not mix?” At the end of the class you will hopefully see that the reason oil and water do not mix is quite distinct from the reason many other substance do not mix. You will also see that the hydrophobic effect is part of a family of processes called “entropy driven ordering” and that the hydrophobic effect has nothing to do with bonds between hydrophobic molecules. This should sound a bit strange to you right now, but I am sure that at the end of the class it will all make sense to you. Why most liquids mix or do not mix (the generic case) What would our physico-chemical intuition tell us about the process of mixing two liquids? Lets think of a simple lattice model for the two solutions. If we call the substances A and B, the energy for mixing should then be the energy of interaction that are made between A and B, minus the energy of interactions that A made with A, and B made with B, plus the entropy of mixing. "Gmixing = "Hmixing # T"Smixing where "Hmixing = 2"Ha#b # "Ha#a # "Hb#b What predictions would this simple model for solutions make for the energetics of mixing? First, mixing should be favored by entropy and therefore the tendency to mix ! should increase with temperature.
    [Show full text]
  • Characterizing Hydrophobicity of Amino Acid Side Chains in a Protein Environment Via Measuring Contact Angle of a Water Nanodroplet on Planar Peptide Network
    Characterizing hydrophobicity of amino acid side chains in a protein environment via measuring contact angle of a water nanodroplet on planar peptide network Chongqin Zhua,b,1, Yurui Gaoa,1, Hui Lic,d,1, Sheng Mengc,d,e, Lei Lia, Joseph S. Franciscoa,2, and Xiao Cheng Zenga,b,2 aDepartment of Chemistry, University of Nebraska−Lincoln, Lincoln, NE 68588; bBeijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China; cBeijing National Laboratory for Condensed Matter Physics, Chinese Academy of Sciences, Beijing 100190, China; dInstitute of Physics, Chinese Academy of Sciences, Beijing 100190, China; and eCollaborative Innovation Center of Quantum Matter, Beijing 100190, China Contributed by Joseph S. Francisco, September 30, 2016 (sent for review September 1, 2016; reviewed by Liem Dang and Wei Yang) Hydrophobicity of macroscopic planar surface is conventionally char- of water droplets on the surface. This conventional method is not acterized by the contact angle of water droplets. However, this feasible for proteins, however, due to its high curvature and nano- engineering measurement cannot be directly extended to surfaces of scale size (38–40). Because of this experimental limitation, instead proteins, due to the nanometer scale of amino acids and inherent of measuring CA, researchers have developed other indirect nonplanar structures. To measure the hydrophobicity of side chains of methods to characterize relative hydrophobicity of amino acid proteins quantitatively, numerous parameters were developed to residues. One of widely used methods is based on a partition of characterize behavior of hydrophobic solvation. However, consistency amino acids in two immiscible liquid phases (8–16).
    [Show full text]
  • The Hydrogen Bond and Its Surroundings Part 2. the Hydrophobic-Bond-Myth
    Chem-Bio Informatics Journal, Vol.18, pp.10-20 (2018) Myths in Modern Science: The Hydrogen Bond and its Surroundings Part 2. The Hydrophobic-Bond-Myth Motohiro Nishio The CHPI Institute, 794-7-910 Izusan, Atami, Shizuoka, Japan E-mail [email protected] (Received September 19; accepted November 29, 2017; published online January 30, 2018) Abstract The fashionable but stereotypic thinking on the concept of the so-called “hydrophobic bond” has been examined in light of criticisms raised by many scientists: Hildebrand, Shinoda, Israelachvili, and so on. The author’s comments are given on the harmful influence of the concept of “hydrophobic bond” in chemistry and biochemistry. In my opinion, this concept can be considered as a myth in modern science. Key Words: proteins, hydrogen bond, nonpolar side-chain, Gibbs free energy Area of Interest: In silico drug discovery 10 Licensed under a Creative Commons Attribution 4.0 International(CC BY 4.0) Chem-Bio Informatics Journal, Vol.18, pp.10-20 (2018) 1. What is the Hydrophobic Bond? They were like two drops of oil that have dripped on to the surface of a basin of water. The drops gathered in one place by repelling water; it is more accurate to say that the pressure of water forces them to adhere to each other, making it impossible for either to get away. The above phrases come from Natsume Soseki’s1 novel “Mon,” The Gate.2 In this context we realize that water pushes oil molecules to adhere to each other, but not that oil molecules dislike water.
    [Show full text]