Computational Molecular Biology: Leszczynski: 9780444500304: Book: : eCampus.com

This book covers applications of computational techniques to biological problems. These techniques are based by an ever-growing number of researchers with different scientific backgrounds - biologists, chemists, and physicists.

The rapid development of molecular biology in recent years has been mirrored by the rapid development of computer hardware and software. This has resulted in the development of sophisticated computational techniques and a wide range of computer simulations involving such methods. Among the areas where progress has been profound is in the modeling of DNA structure and function, the understanding at a molecular level of the role of solvents in biological phenomena, the calculation of the properties of molecular associations in aqueous solutions, computationally assisted drug design, the prediction of protein structure, and protein - DNA recognition, to mention just a few examples. This volume comprises a balanced blend of contributions covering such topics. They reveal the details of computational approaches designed for biomoleucles and provide extensive illustrations of current applications of modern techniques.

A broad group of readers ranging from beginning graduate students to molecular biology professions should be able to find useful contributions in this selection of reviews.

Designed to cover selected examples of the most notable applications of computational techniques to biological problems. Reveals the details of computational approaches designed for biomolecules and provides extensive illustrations of current applications of modern techniques.

Hybrid potentials for large molecular systems

(34)

P. Amara

M.J. Field

Introduction

(4)

Hybrid Potentials

(6)

Challenges

(11)

Treatment of covalent interactions at the QM/MM interface

(6)

Including MM polarization

(2)

Extending the QM region

(2)

Applications

(6)

Lactate and malate dehydrogenases

(1)

Acetylcholinesterase

(1)

Chorismate mutase

(1)

Carbonic anhydrase

(1)

Ni-Fe hydrogenase

(1)

Tyrosine phosphatase

(1)

HIV protease

(1)

Aspartylglucosaminidase and triosephosphate isomerase

(1)

Other systems

(1)

Conclusions

(7)

Proton transfer in models biomolecules, S. Scheiner

(50)

Introduction

(2)

Intrinsic proton transfer properties

(3)

Hydrogen bond length

(8)

Hydrogen bond flexibility

(4)

Asymmetric hydrogen bonds

(3)

Hydrogen bond angles

(6)

Intramolecular H-bonds

(3)

Intermolecular H-bonds

(3)

Reversals in relative pKa

(3)

Environmental effects

(8)

External ions

(4)

Surrounding dipoles

(1)

Polarizable dielectric medium

(3)

Very strong hydrogen bonds

(20)

Computational approaches to the studies of the interactions of nucleic acid bases

(34)

J. Sponer

P. Hobza

J. Leszczynski

Introduction

(3)

Historical overview of ab initio studies on nucleic acid base pairs

(3)

Methods

(5)

Levels of ab initio treatment of base pairs

(1)

Choice of basis set

(1)

Evaluation of interaction energies

(2)

Basis set superposition error

(1)

Geometry optimization

(1)

Results

(17)

Structures of H-bonded DNA base pairs

(3)

Energies of H-bonded DNA base pairs

(3)

Base stacking interactions

102

(6)

Interactions of amino groups of bases

108

(1)

Interactions of bases and base pairs with metal cations

109

(4)

Concluding remarks

113

(6)

Nucleic acid bases in solution

119

(48)

M. Orozco

E. Cubero

X. Barril

C. Colominas

F.J. Luque

The solvent

119

(7)

Computational approaches to solvation

126

(13)

Pure classical methods

128

(8)

Mixed methods

136

(3)

The effect of solvent on nucleic acid bases

139

(20)

The solvation of nucleic acid bases

139

(2)

The effect of solvent on the molecular geometry

141

(4)

Molecular topology

145

(5)

Reactive properties

150

(5)

Intermolecular interactions in nucleic acid bases

155

(4)

Conclusion

159

(8)

Current trends in modeling interactions of DNA fragments with polar solvents

167

(44)

L. Gorb

J. Leszczynski

Introduction

167

(2)

Continuum models of solvation

169

(8)

The family of PCM models

169

(1)

The family of SCRF models

170

(2)

The dispersion forces

172

(2)

The cavitation forces

174

(1)

SMx family of solvation models

175

(2)

Supermolecular approximation

177

(1)

The hydration of the prototypic molecules

177

(6)

The hydration of heterocycles---parent compounds of DNA bases

183

(5)

Hydration of the DNA bases

188

(12)

Structural parameters of the monohydrated DNA bases

188

(5)

Structural parameters of the polyhydrated DNA bases

193

(1)

Relative stability

194

(3)

Intramolecular proton transfer

197

(3)

Hydration of DNA base pairs

200

(4)

Conclusion

204

(7)

Radiation-induced DNA damage and repair: An approach from ab initio MO method

211

(34)

M. Aida

M. Kaneko

M. Dupuis

Introduction

211

(3)

Structures of pyrimidine dimers

214

(2)

Characteristics of thymine dimer

216

(4)

Methods

216

(1)

Ionization potential of T<>T

216

(2)

Structural characteristics of T<>T and T<>(•+)

218

(2)

Fragmentation mechanism of T<>T(•+)

220

(11)

Methods

220

(1)

Structure of thymine dimer radical cation at CAS(3e+4o)

221

(1)

Fragmentation pathway

222

(4)

Initial thymine dimer radical cation

226

(1)

Structural change and spin distribution change along the fragmentation path

227

(1)

Comparison with the case of (C2H4)2 •+ complex

228

(1)

Comparison with experiments

229

(1)

T<>T(•+) dissociation in DNA

229

(2)

Other pyrimidine dimers

231

(10)

Methods

231

(1)

Structural and electronical characteristics of pyrimidine dimers

231

(10)

Conclusion

241

(4)

Application of molecular orbital theory to elucidation of radical processes induced by radiation damage to DNA

245

(34)

A.-O. Colson

M.D. Sevilla

Background

245

(2)

Role of theory

247

(1)

Individual DNA bases

247

(4)

DNA base ionization potentials

248

(2)

DNA base electron affinities

250

(1)

Base pairs

251

(2)

Hydrogen bonding

251

(1)

Proton transfer processes in neutral and ion radical base pairs

252

(1)

Base pair ionization potentials

253

(1)

Base pair electron affinities

253

(1)

Base pair stacking

253

(2)

Effect of waters of hydration

255

(3)

Solvation effects on ionization potentials

255

(3)

Solvation effects on electron affinities

258

(1)

Sugar-phosphate backbone

258

(3)

Phosphate radicals in DNA

258

(1)

Deoxyribose radicals in DNA

259

(1)

Ionization potentials of base, deoxyribose and phosphate portions of DNA

260

(1)

DNA base H• and •OH adduct radicals

261

(9)

Electron affinities of neural adduct radicals

262

(3)

Ionization potentials of neural adduct radicals

265

(1)

Redox potentials of neural adduct radicals

265

(1)

Energetics of radical reactions initiated by radiolytic damage to DNA

266

(2)

Structural features of base adduct radicals

268

(2)

Radioprotection

270

(9)

Methyl mercaptan and cysteamine

270

(9)

Exploring the structural repertoire of Guanine-rich DNA sequences: Computer modelling studies

279

(46)

M. Bansal

M. Ravikiran

S. Chowdhury

Introduction

279

(2)

Guanine rich triple helical structures

281

(17)

Model building of d(C)12 •d(G)12 triple helices

284

(1)

Protocol for molecular dynamics of (C)12 •d(G)12 *d(G)12 triple helices

285

(1)

Structural parameters for (C)12 •d(G)12 *d(G)12 triple helices

286

(3)

Analysis of structural variability in (C)12 *d(G)12 *d(G)12 triplexes

289

(9)

Parallel and folded back quadruplex structures

298

(19)

Protocol for molecular dynamics of d(G)7 quadruplex structures

301

(1)

Structural analysis of d(G)7 parallel quadruplex structures

302

(15)

Conclusions

317

(8)

Third strand can be in either orientation in (C)12 *d(G)12*d(G)12 triplex

317

(1)

Intercalated ions make the G-quadruplex structure rigid and stable

318

(7)

The calculation of relative binding thermodynamics of molecular associations in aqueous environments

325

(44)

G.J. Tawa

I.A. Topol

S.K. Burt

Introduction

326

(6)

Theory

332

(6)

Fundamental statistical mechanical derivation of the relative binding free energy

332

(3)

Special considerations regarding ligands binding to HIV-1 protease

335

(3)

Computational protocol

338

(6)

The relative binding free energies of peptidic inhibitors to HIV-1 protease and its 184V mutant

344

(7)

Protonation states of the ASP 25, 125 dyad

344

(1)

The thermodynamics of binding

345

(6)

Concluding remarks

351

(18)

Theoretical tools for analysis and modelling electrostatic effects in biomolecules

369

(28)

W.A. Sokalski

P. Kedzierski

J. Grembecka

P. Dziekonski

K. Strasburger

Introduction

369

(1)

Methods

370

(11)

Hybrid variation-perturbation decomposition of SCF interaction energy

370

(4)

Electrostatic interactions

374

(5)

Differential transition state/product stabilization approach

379

(2)

Applications

381

(10)

Nonempirical analysis of pKa shifts in mutated subtilisines

381

(1)

Physical nature of the solvent induced proton transfer

382

(1)

Analysis of reactant interactions in ribonuclease A active site

383

(1)

Electrostatic nature of catalytic activity in aminoacyl t-RNA synthetases

384

(3)

Electrostatic nature of inhibitor binding in leucine aminopeptidase

387

(4)

Conclusions

391

(6)

Application of reduced models to protein structure prediction

397

(44)

J. Skolnick

A. Kolinski

A.R. Ortiz

Introduction

397

(7)

Energy functions and search protocols

398

(1)

Protein representation

398

(2)

Use of simplified models to obtain general insights into protein folding

400

(1)

Threading approaches to tertiary structure prediction

401

(1)

Exact restraint models of proteins

402

(1)

Restraint free ab initio protein folding

402

(1)

Evolutionary-based approaches to protein structure prediction

403

(1)

Exact restraint models

404

(11)

Secondary and tertiary restraints in assembly of protein structures

404

(2)

Models with exact secondary structure but no tertiary restraints

406

(3)

Models with exact but loose secondary structure and tertiary restraints

409

(5)

How can these approaches be integrated with experiment

414

(1)

Tertiary structure predictions by ab initio model building

415

(11)

Predictions by restraint free folding

415

(3)

Prediction by restraint driven folding: Evolutionary based approaches

418

(8)

Limitations and outlook

426

(1)

What is the requisite resolution of predicted structures?

426

(1)

Techniques for low to high resolution modelling

427

(2)

Role of structure prediction in the genomics revolution

429

(1)

Outlook

430

(11)

Modelling DNA-protein interactions

441

(44)

K. Zakrzewska

R. Lavery

The first steps

441

(1)

Analysing protein-DNA recognition

442

(20)

Geometry

445

(3)

Electrostatics

448

(4)

Thermodynamics

452

(10)

Molecular mechanics and dynamics simulations

462

(13)

Transcription factors

463

(1)

Hormone receptors

464

(4)

Minor groove binding proteins

468

(4)

Larger scale modelling

472

(3)

Protein-DNA docking

475

(3)

The next steps

478

(7)

Interactions of small molecules and peptides with membranes

485

(52)

A. Pohorille

M.A. Wilson

C. Chipot

M.H. New

K. Schwieghofer

Introduction

485

(3)

Approach

488

(6)

Transport of small solutes and ions across membrane interfaces

494

(13)

Small, neutral solutes in membranes

495

(7)

Unassisted transport of ions across membranes

502

(5)

Interactions of peptides and membranes

507

(15)

Peptides at aqueous interfaces

507

(6)

Peptides in membranes

513

(4)

Simulations of transmembrane channels

517

(5)

Hydration forces

522

(4)

Conclusions and future directions

526

(11)

Modeling of antifreeze proteins

537

(32)

J.D. Madura

A. Wierzbicki

Introduction

537

(2)

Modeling AFPS on ice

539

(13)

Winter Flounder on the (201)

539

(1)

Shorthorn Sculpin on the (2-1 0)

540

(8)

Sea Raven on the (111)

548

(2)

Ocean Eel Pout on the (100)

550

(2)

Simulations of AFPS with explicit water

552

(4)

Shorthorn Sculpin in a rectangular box

552

(2)

Sea Raven in truncated Octahedron

554

(1)

Ocean Eel Pout in a periodic box

555

(1)

Simulations of AFPS in a continuum

556

(7)

Shorthorn Sculpin

557

(3)

Ocean Eel Pout

560

(3)

Simulations of the Winter Flounder at the ice/water interface

563

(2)

Summary

565

(4)

The role of computational techniques in retrometabolic drug design strategies

569

(50)

N. Bodor

P. Buchwald

M.-J. Huang

Introduction

569

(1)

Principles of retrometabolic drug design

570

(2)

Predicting properties

572

(10)

Molecular size

573

(2)

Octanol-water partition coefficient

575

(6)

Water solubility

581

(1)

Soft drugs

582

(10)

Soft anticholinergics

584

(4)

Soft β-blockers

588

(4)

Computer-aided design

592

(10)

Structure generation

593

(1)

Ranking

594

(2)

Illustration of computer-aided soft drug design

596

(6)

Chemical delivery systems

602

(11)

Brain-targeting chemical delivery systems

602

(3)

Predicting partition properties

605

(1)

Cyclodextrin complexes

606

(7)

Conclusions

613

(6)

Computational aspects of neural membrane biophysics

619

(20)

R. Wallace

Introduction

619

(2)

Algorithmic complexity and the principles of molecular computing

621

(5)

Linear superposition permits massive parallelism

623

(1)

Transduction and amplification require macroscopic-microscopic informational state-space mapping

624

(1)

Memory is constrained by quantum recurrence

625

(1)

Membrane studies in cell biology

626

(2)

Hydrophobic mismatch: a candidate mechanism for neuromolecular computing

628

(1)

Hydrophobic mismatch and molecular computation

629

(1)

Genetic regulation of neuromolecular computing

630

(1)

Potential experiments in neuromolecular computation

631

(2)

Conclusion

633

(6)

Index

639


	Buy Textbooks Sell Textbooks College Apparel Shop by School Virtual Bookstores	Order Status Shipping Rates Return Policy Marketplace Info F.A.S.T.	Contact Us Privacy Policy Legal Notices Site Security Employment	Help Desk eCampus Blog Affiliate Program Bulk Orders College Marketing

Need Help? eService@ecampus.com Copyright© 1999-2008
.