DOI: 10.1002/cphc.200700857. (Thermo)dynamic Role of Receptor Flexibility, Entropy, and Motional Correlation in Protein

(Thermo)dynamic Role of Receptor Flexibility, Entropy, and Motional Correlation in Protein–Ligand Binding

10.1002/cphc.200700857

Crossref journal-article

Wiley

ChemPhysChem (311)

Abstract

AbstractThe binding of 2‐amino‐5‐methylthiazole to the W191G cavity mutant of cytochrome c peroxidase is an ideal test case to investigate the entropic contribution to the binding free energy due to changes in receptor flexibility. The dynamic and thermodynamic role of receptor flexibility are studied by 50 ns‐long explicit‐solvent molecular dynamics simulations of three separate receptor ensembles: W191G binding a K+ ion, W191G–2a5mt complex with a closed 190–195 gating loop, and apo with an open loop. We employ a method recently proposed to estimate accurate absolute single‐molecule configurational entropies and their differences for systems undergoing conformational transitions. We find that receptor flexibility plays a generally underestimated role in protein–ligand binding (thermo)dynamics and that changes of receptor motional correlation determine such large entropy contributions.

Bibliography

Baron, R., & McCammon, J. A. (2008). (Thermo)dynamic Role of Receptor Flexibility, Entropy, and Motional Correlation in ProteinâLigand Binding. ChemPhysChem, 9(7), 983â988. Portico.

Authors 2

Riccardo Baron (first)
J. Andrew McCammon (additional)

References 57 Referenced 35

{'key': 'e_1_2_6_1_2', 'volume-title': 'Molecular Foundations of Drug‐Receptor Interaction', 'author': 'Dean P. M.', 'year': '1987'} / Molecular Foundations of Drug‐Receptor Interaction by Dean P. M. (1987)
10.1002/ange.19941062306
10.1002/anie.199423751
10.1017/CBO9780511524837
10.1002/ange.19961082205
10.1002/anie.199625881
10.1002/(SICI)1521-3757(19990315)111:6<778::AID-ANGE778>3.0.CO;2-C
10.1002/(SICI)1521-3773(19990315)38:6<736::AID-ANIE736>3.0.CO;2-R
{'key': 'e_1_2_6_6_2', 'volume-title': 'Drug‐Receptor Thermodynamics: Introduction and Applications', 'year': '2001'} / Drug‐Receptor Thermodynamics: Introduction and Applications (2001)
10.1002/1521-3757(20020802)114:15<2764::AID-ANGE2764>3.0.CO;2-I
10.1002/1521-3773(20020802)41:15<2644::AID-ANIE2644>3.0.CO;2-O
10.1126/science.1096361
10.1002/pro.5560040919
10.1038/nsb0796-626
10.1021/bi9708038
10.1006/jmbi.2001.5287
10.1016/j.jmb.2006.01.034
10.1021/bi700866x
{'key': 'e_1_2_6_15_2', 'first-page': '171', 'volume': '16', 'author': 'Bosshard H. R.', 'year': '2001', 'journal-title': 'News Physiol. Sci.'} / News Physiol. Sci. by Bosshard H. R. (2001)
10.1016/S1367-5931(02)00341-1
10.1021/jm0341913
{'key': 'e_1_2_6_18_2', 'volume-title': 'Thermodynamics', 'author': 'Fermi E.', 'year': '1936'} / Thermodynamics by Fermi E. (1936)
{'key': 'e_1_2_6_19_2', 'volume-title': 'Fundamentals of Statistical and Thermal Physics', 'author': 'Reif F.', 'year': '1985'} / Fundamentals of Statistical and Thermal Physics by Reif F. (1985)
In this work usage of the terms “flexibility” “dynamics” “thermodynamics” “single‐molecule” and “molecular” is based on their statistical mechanics definitions. Dynamics is related to phase‐space sampling. Thermodynamics concerns the sampled configurational space only that is configurations not momenta (see refs. [18 19]). For example different dynamics due to different degrees of freedom momenta and frequencies may still correspond to identical thermodynamic properties. Flexibility involves both aspects and generally refers to ensemble average properties only (e.g. mean‐square fluctuations of a molecular system). For a definition of single‐molecule and molecular entropy terms see ref. [35].
10.1021/ja00074a073
10.1016/S1367-5931(99)00008-3
10.1038/70008
10.1021/ar000079c
10.1002/cbic.200500010
10.1038/nature05959
10.1006/jmbi.1994.1430
10.1016/S0006-3495(97)78756-3
10.1021/ar950181n
10.1063/1.1636153
10.1016/S0006-3495(04)74084-9
10.1016/j.bbapap.2005.07.041
10.1021/jp046022f
10.1039/b608486a
10.1021/jp055888y
{'key': 'e_1_2_6_36_2', 'first-page': '87', 'volume': '11', 'author': 'Baron R.', 'year': '2006', 'journal-title': 'Trends Phys. Chem.'} / Trends Phys. Chem. by Baron R. (2006)
10.1002/cphc.200600658
10.1073/pnas.0610494104
10.1002/ange.200502655
10.1002/anie.200502655
10.1006/jmbi.2001.5202
10.1002/prot.21180
10.1002/jcc.20580
10.1529/biophysj.106.081539
10.1021/jp061627s
10.1529/biophysj.107.0900157
10.1002/jcc.20303
W. F. van Gunsteren S. R. Billeter A. A. Eising P. H. Hünenberger P. Krüger A. E. Mark W. R. P. Scott I. G. Tironi Biomolecular Simulation: The GROMOS96 Manual and User Guide vdf Hochschulverlag AG an der ETH Zurich/BIOMOS b.v. Groningen Zurich/Groningen 1996.
10.1002/jcc.20193
10.1021/j100384a009
10.1007/978-94-015-7658-1_21
10.1002/jcc.20071
10.1016/0022-2836(79)90308-5

Dates

Type	When
Created	17 years, 4 months ago (April 16, 2008, 10:47 a.m.)
Deposited	1 year, 10 months ago (Oct. 10, 2023, 11:22 p.m.)
Indexed	1 year ago (Aug. 12, 2024, 7:12 a.m.)
Issued	17 years, 4 months ago (April 28, 2008)
Published	17 years, 4 months ago (April 28, 2008)
Published Online	17 years, 4 months ago (April 28, 2008)
Published Print	17 years, 3 months ago (May 16, 2008)

Funders 0

None

BibTeX

@article{Baron_2008, title={(Thermo)dynamic Role of Receptor Flexibility, Entropy, and Motional Correlation in Protein–Ligand Binding}, volume={9}, ISSN={1439-7641}, url={http://dx.doi.org/10.1002/cphc.200700857}, DOI={10.1002/cphc.200700857}, number={7}, journal={ChemPhysChem}, publisher={Wiley}, author={Baron, Riccardo and McCammon, J. Andrew}, year={2008}, month=apr, pages={983–988} }

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