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Principles of Biomolecular Recognition

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Recognition Receptors in Biosensors

Abstract

Biomolecular recognition, the process by which biomolecules recognize and bind to their molecular targets, typically highly specific, high affinity and reversible, and is generalizable to an effectively unlimited range of aqueous analytes. Consequently, it has been exploited in a wide range of diagnostic and synthetic technologies. Biomolecular recognition is typically driven by many weak interactions working in concert. The most important of these interactions include (i) the electrostatic interaction due to permanent charges, dipoles, and quadrupoles, (ii) the polarization of charge distributions by the interaction partner leading to induction and dispersion forces, (iii) Pauli-exclusion principle-derived inter-atomic repulsion, and (iv) a strong, “attractive” force arising largely from the entropy of the solvent and termed the hydrophobic effect. Because the aqueous environment significantly reduces the impact of electrostatic and induction interactions, the hydrophobic effect is often the dominant force stabilizing the formation of correct biomolecule–target complexes. The other effects are nevertheless important in defining the specificity of the macromolecule toward its target by destabilizing binding events in which a less-than-ideal network of interactions between two partners would be established.

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Abbreviations

CCSD:

Coupled cluster singles and doubles

DNA:

Deoxyribonucleic acid

MP2:

M½ller–Plesset perturbation theory of the second order

NMR:

Nuclear magnetic resonance

RNA:

Ribonucleic acid

TIP4P:

Transferable intermolecular potential–4 point

ΔG :

Free energy change

ΔU :

Internal energy change

ΔS :

Entropy change

ΔH :

Enthalpy change

ΔV :

Volume change

R :

Universal gas constant

T :

Absolute temperature

F :

Force

q i :

Charge on particle i

ε0 :

Dielectric permittivity of vacuum

r :

Distance between the centers of two objects

μ :

Dipole moment

k :

Boltzmann constant

Θ:

Quadrupole moment

α:

Polarizability

I i :

First ionization potential of atom or molecule i

σ:

Size parameter in the Lennard-Jones potential

ε :

Softness parameter in the Lennard Jones potential; dielectric constant

h :

Planck constant

v :

Vibrational frequency; effective volume of the molecule

σ:

Rotational symmetry number

λB :

Bjerrum length

N A :

Avogadro constant

n i :

Refractive index of solute i.

References

  • Aragones JL, Noya EG, Abascal JLF, Vega C (2007) Properties of ices at 0 K: A test of water models. J Chem Phys 127:154518

    Google Scholar 

  • Balzani V, Clemente-Leon M, Credi A, Ferrer B, Venturi M, Flood AH, Stoddart JF (2006) Autonomous artificial nanomotor powered by sunlight. Proc Natl Acad Sci USA 103:1178–1183

    Article  Google Scholar 

  • Bayer Y, Fasshauer M, Paschke R (2004) The novel missense mutation methionine 442 threonine in the thyroid hormone receptor beta causes thyroid hormone resistance: a case report. Exp Clin Endocrinol Diabetes 112:95–97

    Article  Google Scholar 

  • Bolger MB, Jorgensen EJ (1980) Molecular interactions between thyroid hormone analogs and the rat liver nuclear receptor. Partitioning of equilibrium binding free energy changes into substituent group interactions. J Biol Chem 255:10271–10278

    Google Scholar 

  • Bruice TC, Bradbury WC (1968) The gem effect. IV. Activation parameters accompanying the increased steric requirements of 3, 3′-substituents in the solvolysis of mono(p-bromophenyl) glutarates. J Am Chem Soc 90:3808–3812

    Article  Google Scholar 

  • Bruice TC, Pandit UK (1960) The effect of geminal substitution, ring size, and rotamer distribution on the intramolecular nucleophilic catalysis of the hydrolysis of monophenyl esters of dibasic acids and the solvolysis of the intermediate anhydrides. J Am Chem Soc 82:5858–5865

    Article  Google Scholar 

  • Buckingham AD, Del Bene JE, McDowell SAC (2008) The hydrogen bond. Chem Phys Lett 463:1–10

    Article  Google Scholar 

  • Burley SK, Petsko GA (1986) Amino–aromatic interactions in proteins. FEBS Lett 203:139–143

    Article  Google Scholar 

  • Cabani S, Gianni P, Mollica V, Lepori L (1981) Group contributions to the thermodynamic properties of nonionic organic solutes in dilute aqueous solution. J Solution Chem 10:563–595

    Article  Google Scholar 

  • Chalikian TV, Filfil R (2003) How large are the volume changes accompanying protein transitions and binding? Biophys Chem 104:489–499

    Article  Google Scholar 

  • Chang CA, Chen W, Gilson MK (2007) Ligand configurational entropy and protein binding. Proc Natl Acad Sci USA 104:1534–1539

    Article  Google Scholar 

  • Cramer F (1995) Biochemical correctness: Emil Fischer’s lock and key hypothesis, a hundred years after – an essay. Pharm Acta Helv 69:193–203

    Article  Google Scholar 

  • Dougherty DA (1996) Cation–π interactions in chemistry and biology: a new view of benzene, Phe, Tyr, and Trp. Science 271:163–168

    Article  Google Scholar 

  • Eisenberg D, McLachlan AD (1986) Solvation energy in protein folding and binding. Nature 319:199–203

    Article  Google Scholar 

  • Erbil HY (2006) Surface chemistry of solid and liquid interfaces. Wiley-Blackwell, New York

    Google Scholar 

  • Feller D (1999) Strength of the benzene–water hydrogen bond. J Phys Chem A 103:7558–7561

    Article  Google Scholar 

  • Finkelstein AV, Janin J (1989) The price of lost freedom: entropy of bimolecular complex formation. Protein Eng 3:1–3

    Article  Google Scholar 

  • Fischer E (1894) Einfluss der Configuration auf die Wirkung der Enzyme. Ber 27:2985–2993

    Google Scholar 

  • Freire E (2005) A thermodynamic guide to affinity optimization of drug candidates. Protein Rev 3:291–307

    Article  Google Scholar 

  • Frommel C (1984) The apolar surface area of amino acids and its empirical correlation with hydrophobic free energy. J Theor Biol 111:247–260

    Article  Google Scholar 

  • Gadhi J, Lahrouni A, Legrand J, Demaison J (1995) Dipole moment of CH3CN. J Chim Phys Phys – Chim Biol 92:1984–1992

    Google Scholar 

  • Gregory JK, Clary DC, Liu K, Brown MG, Saykally RJ (1997) The water dipole moment in water clusters. Science 275:814–817

    Article  Google Scholar 

  • Grzesiek S, Cordier F, Jaravine V, Barfield M (2004) Insights into biomolecular hydrogen bonds from hydrogen bond scalar couplings. Prog Nucl Magn Reson Spectrosc 45:275–300

    Article  Google Scholar 

  • Gubskaya AV, Kusalik PG (2002) The total molecular dipole moment for liquid water. J Chem Phys 117:5290–5302

    Article  Google Scholar 

  • Guillot B (2002) A reappraisal of what we have learnt during three decades of computer simulations on water. J Mol Liq 101:219–260

    Article  Google Scholar 

  • Hamaker HC (1937) The London–van der Waals attraction between spherical particles. Physica 4:1058–1072

    Article  Google Scholar 

  • Hunter CA, Lawson KR, Perkins J, Urch CJ (2001) Aromatic interactions. J Chem Soc Perkin Trans 2:651–669

    Google Scholar 

  • Isaacs ED, Shukla A, Platzman PM, Hamann DR, Barbiellini B, Tulk CA (1999) Covalency of the hydrogen bond in ice: A direct X-ray measurement. Phys Rev Lett 82:600–603

    Article  Google Scholar 

  • Israelachvili JN (1992) Intermolecular and surface forces, 2nd edn. Academic Press, New York

    Google Scholar 

  • Jiang L, Althoff EA, Clemente FR, Doyle L, Röthlisberger D, Zanghellini A, Gallaher JL, Betker JL, Tanaka F, Barbas CFI, Hilvert D, Houk KN, Stoddard BL, Baker D (2008) De novo computational design of retro-aldol enzymes. Science 319:1387–1391

    Article  Google Scholar 

  • Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML (1983) Comparison of simple potential functions for simulating liquid water. J Chem Phys 79:926–935

    Article  Google Scholar 

  • Kestner NR, Sinanoğlu O (1965) Intermolecular forces in dense media. Discuss Faraday Soc 40:266–267

    Article  Google Scholar 

  • Ko YH, Kim E, Hwang I, Kim K (2007) Supramolecular assemblies built with host-stabilized charge-transfer interactions. Chem Commun 13:1305–1315

    Article  Google Scholar 

  • Leavitt S, Freire E (2001) Direct measurement of protein binding energetics by isothermal titration calorimetry. Curr Opin Struct Biol 11:560–566

    Article  Google Scholar 

  • Lee S-L, Alexander R, Smallwood A, Trievel R, Mersinger L, Weber PC, Kettner C (1997) New inhibitors of thrombin and other trypsin-like proteases: Hydrogen bonding of an aromatic cyano group with a backbone amide of the P1 binding site replaces binding of a basic side chain. Biochemistry 36:13180–13186

    Article  Google Scholar 

  • Lii J-H, Allinger NL (2008) The important role of lone-pairs in force field (MM4) calculations on hydrogen bonding in alcohols. J Phys Chem A 112:11903–11913

    Article  Google Scholar 

  • London F (1937) The general theory of molecular forces. Trans Faraday Soc 33:8–26

    Article  Google Scholar 

  • Ma JC, Dougherty DA (1997) The Cation–π Interaction. Chem Rev 97:1303–1324

    Article  Google Scholar 

  • Magnasco V, Battezzati M, Rapallo A, Costa C (2006) Keesom coefficients in gases. Chem Phys Lett 428:231–235

    Article  Google Scholar 

  • Manohar S, Atkinson G (1993) The effect of high pressure on the ion pair equilibrium constant of alkali metal fluorides: a spectrophotometric study. J Solution Chem 22:859–872

    Article  Google Scholar 

  • McLachlan AD (1965) Effect of the medium on dispersion forces in liquids. Discuss Faraday Soc 40:239–245

    Article  Google Scholar 

  • McQuarrie DA (2000) Statistical Mechanics, 2nd edn. University Science Books, Sausalito, CA

    MATH  Google Scholar 

  • Mecozzi S, Rebek J Jr (1998) The 55% solution: a formula for molecular recognition in the liquid state. Chem Eur J 4:1016–1022

    Article  Google Scholar 

  • Ngola SM, Dougherty DA (1996) Evidence for the importance of polarizability in biomimetic catalysis Involving cyclophane receptors. J Org Chem 61:4355–4360

    Article  Google Scholar 

  • Olsson TSG, Williams MA, Pitt WR, Ladbury JE (2008) The thermodynamics of protein-ligand interaction and solvation: insights for ligand design. J Mol Biol 384:1002–1017

    Article  Google Scholar 

  • Plokhotnichenko AM, Radchenko ED, Stepanian SG, Adamowicz L (1999) p-Quinone dimers: H-bonding vs. stacked interaction. Matrix-isolation infrared and ab initio study. J Phys Chem A 103:11052–11059

    Article  Google Scholar 

  • Ramos S, Neilson GW, Barnes AC, Buchanan P (2005) An anomalous X-ray diffraction study of the hydration structures of Cs+ and I− in concentrated solutions. J Chem Phys 123:214501–214510

    Article  Google Scholar 

  • Romero AH, Silvestrelli PL, Parrinello M (2001) Compton scattering and the character of the hydrogen bond in ice Ih. J Chem Phys 115:115–123

    Article  Google Scholar 

  • Sandler B, Webb P, Apriletti JW, Huber BR, Togashi M, Lima STC, Juric S, Nilsson S, Wagner R, Fletterick RJ, Baxter JD (2004) Thyroxine–thyroid hormone receptor interactions. J Biol Chem 279:55801–55808

    Article  Google Scholar 

  • Siebert X, Amzel LM (2003) Loss of translational entropy in molecular associations. Proteins: Struct Funct Bioinf 54:104–115

    Article  Google Scholar 

  • Southall NT, Dill KA, Haymet ADJ (2002) A view of the hydrophobic effect. J Phys Chem B 106:521–533

    Article  Google Scholar 

  • Stone AJ (1996) The theory of intermolecular forces. Oxford University Press, New York

    Google Scholar 

  • Stone AJ (2008) Intermolecular potentials. Science 321:787–789

    Article  Google Scholar 

  • Sunner J, Nishizawa K, Kebarle P (1981) Ion–solvent molecule interactions in the gas phase. The potassium ion and benzene. J Phys Chem 85:1814–1820

    Article  Google Scholar 

  • Tamura A, Privalov PL (1997) The entropy cost of protein association. J Mol Biol 273:1048–1060

    Article  Google Scholar 

  • Tidor B, Karplus M (1994) The contribution of vibrational entropy to molecular association. The dimerization of insulin. J Mol Biol 238:405–414

    Article  Google Scholar 

  • Tsuzuki S, Yoshida M, Uchimaru T, Mikami M (2001) The origin of the cation/π interaction: the significant importance of the induction in Li+ and Na+ complexes. J Phys Chem A 105:769–773

    Article  Google Scholar 

  • Williams JH (1993) The molecular electric quadrupole moment and solid-state architecture. Acc Chem Res 26:593–598

    Article  Google Scholar 

  • Yoshii N, Miura S, Okazaki S (2001) A molecular dynamics study of dielectric constant of water from ambient to sub- and supercritical conditions using a fluctuating-charge potential model. Chem Phys Lett 345:195–200

    Article  Google Scholar 

  • Yu YB, Lavigne P, Kay CM, Hodges RS, Privalov PL (1999) Contribution of translational and rotational entropy to the unfolding of a dimeric coiled-coil. J Phys Chem B 103:2270–2278

    Article  Google Scholar 

  • Yu YB, Privalov PL, Hodges RS (2001) Contribution of translational and rotational motions to molecular association in aqueous solution. Biophys J 81:1632–1642

    Article  Google Scholar 

  • Zacharias N, Dougherty DA (2002) Cation–π interactions in ligand recognition and catalysis. Trends Pharmacol Sci 23:281–287

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, 93106, USA

    Kalju Kahn

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  1. Kalju Kahn
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  2. Kevin W. Plaxco
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Correspondence to Kalju Kahn .

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  1. GDG Environnement Ltée, rue St-Laurent, 2e étage 430, Trois-Rivieres, G8T 6H3, Canada

    Mohammed Zourob

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Kahn, K., Plaxco, K.W. (2010). Principles of Biomolecular Recognition. In: Zourob, M. (eds) Recognition Receptors in Biosensors. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0919-0_1

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  • DOI: https://doi.org/10.1007/978-1-4419-0919-0_1

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