Computational biophysics of membrane proteins

274 Pages·2016·11.405 MB·English

by  Carmen Domene, Carmen Domene, Jonathan Hirst, Mary Luckey, Andrew Pohorille, Simone Furini, Amitabha Chattopadhyay, Ben Corry, Emad Tajkhorshid, Philip Biggin

Computational Biophysics of Membrane Proteins
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RSC Theoretical and Computational Chemistry Series
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Computational Biophysics of
Membrane Proteins
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1 Chapter 1 Introduction to the Structural Biology of Membrane
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n 3 1.5.3 Enzymes 14
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References 17
Chapter 2 Molecular Dynamics Simulations: Principles and
Applications for the Study of Membrane Proteins 19
Victoria Oakes and Carmen Domene
2.1 Introduction 19
2.2 Classical Molecular Dynamics 20
2.2.1 Additive Force Fields 22
2.2.2 Polarisable Force Fields 24
RSCTheoreticalandComputationalChemistrySeriesNo.10
ComputationalBiophysicsofMembraneProteins
EditedbyCarmenDomene
rTheRoyalSocietyofChemistry2017
PublishedbytheRoyalSocietyofChemistry,www.rsc.org
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vi Contents
2.2.3 Practical and Technical Considerations 25
2.2.4 Applications 29
2.3 Coarse-grained Molecular Dynamics
Simulations 30
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3.5.2 Adaptive Biasing Force Method 78
3.6 Replica Exchange for Enhanced Sampling in
Configurational Space 80
3.7 Applications of Free Energy Calculations:
Case Studies 81
3.7.1 Binding of Anesthetic Ligands to
Receptors 82
3.7.2 Free Energies of Ions across Channels 84
3.7.3 Conformational Transitions in Receptors 86
3.8 Non-equilibrium Properties from Free Energy
Calculations 88
3.8.1 Theoretical Background 90
3.8.2 Example – the Leucine–Serine Channel 93
3.9 Summary and Conclusions 96
References 98
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Chapter 4 Non-atomistic Simulations of Ion Channels 107
Claudio Berti and Simone Furini
4.1 Introduction 107
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5.1.1 Membrane Components 138
5.2 Role of Membrane Lipids in Membrane Protein
Organization and Function 139
5.3 Mechanisms for Lipid Regulation of Membrane
Proteins 140
5.3.1 Specific Membrane Effects 140
5.3.2 Non-specific Membrane Effects 142
5.4 Range of Time Scales Exhibited by Membranes 142
5.5 Lipid–Protein Interactions: Insights from
Experimental Approaches 144
5.5.1 DeterminingNear-neighborRelationshipsin
Membranes: Interaction of Melittin with
Membrane Cholesterol utilizing FRET 144
5.5.2 Interaction of the Actin Cytoskeleton with
GPCRs: Application of FRAP 147
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5.6 Computational Approaches to Study Membrane
Organization and Lipid–Protein Interactions 149
5.6.1 Simulating Single Component and
Multi-component Bilayers 151
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6.6.2 Channel Blockage by Small Molecules 187
6.7 Conclusions 189
Acknowledgements 190
References 190
Chapter 7 Computational Characterization of Molecular
Mechanisms of Membrane Transporter Function 197
Noah Trebesch, Josh V. Vermaas and Emad Tajkhorshid
7.1 Membrane Transport – A Fundamental Biological
Process 197
7.2 Substrate Binding and Unbinding 200
7.2.1 Spontaneous Binding Simulations Revealing
a Binding Mechanism and Site 201
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7.2.2 Proposing Substrate Binding Sites through
Molecular Docking 202
7.2.3 Unraveling Substrate Release Pathways 204
7.3 Capturing Localized Transporter Motions with
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Chapter 8 Computational Studies of Receptors 237
Maria Musgaard and Philip C. Biggin
8.1 Introduction 237
8.2 Network Models Can Provide Insight into
Large-scale Conformational Changes 239
8.3 Network Models to Examine Gating 241
8.4 Network Models to Compare Dynamics 242
8.5 Network Models to Suggest Novel Mechanisms
for Modulation 244
8.6 Molecular Dynamics to Aid Crystallographic
Interpretation 245
8.7 Molecular Dynamics to Move between States 247
8.8 Molecular Dynamics to Refine Working
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8.9 Molecular Dynamics to Explain the Effects of
Ions and Water 251
8.10 Molecular Dynamics to Quantify Free Energy
Requirements 253
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