Assessment of the role of computations in structural biology.

Computations are now an integrated part of structural biology and are used in data gathering, data processing, and data storage as well as in a full spectrum of theoretical pursuits. In this review, we focus on areas of great promise and call attention to important issues of internal consistency and error analysis.

[1]  Peter A. Kollman,et al.  Computational alanine scanning of the 1:1 human growth hormone–receptor complex , 2002, J. Comput. Chem..

[2]  A. Palmer,et al.  Nmr probes of molecular dynamics: overview and comparison with other techniques. , 2001, Annual review of biophysics and biomolecular structure.

[3]  A. J. Frank,et al.  Kinetic intermediates in the folding of gaseous protein ions characterized by electron capture dissociation mass spectrometry. , 2001, Journal of the American Chemical Society.

[4]  J. Aqvist,et al.  A new method for predicting binding affinity in computer-aided drug design. , 1994, Protein engineering.

[5]  Alexander D. MacKerell,et al.  Development and current status of the CHARMM force field for nucleic acids , 2000, Biopolymers.

[6]  C. Brooks,et al.  From folding theories to folding proteins: a review and assessment of simulation studies of protein folding and unfolding. , 2001, Annual review of physical chemistry.

[7]  David S. Moss,et al.  Error Estimates of Protein Structure Coordinates and Deviations from Standard Geometry by Full-Matrix Refinement of γB- and βB2-Crystallin , 1998 .

[8]  A. Fersht.  On the simulation of protein folding by short time scale molecular dynamics and distributed computing , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[9]  P. Kollman,et al.  Continuum Solvent Studies of the Stability of DNA, RNA, and Phosphoramidate−DNA Helices , 1998 .

[10]  Walter Cedeño,et al.  On the Use of Neural Network Ensembles in QSAR and QSPR , 2002, J. Chem. Inf. Comput. Sci..

[11]  W. C. Still,et al.  Semianalytical treatment of solvation for molecular mechanics and dynamics , 1990 .

[12]  T. Darden,et al.  Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems , 1993 .

[13]  Harry A. Stern,et al.  Development of a polarizable force field for proteins via ab initio quantum chemistry: First generation model and gas phase tests , 2002, J. Comput. Chem..

[14]  D A Agard,et al.  Computational method for the design of enzymes with altered substrate specificity. , 1991, Journal of molecular biology.

[15]  Zaida Luthey-Schulten,et al.  Folding funnels: The key to robust protein structure prediction , 2002, J. Comput. Chem..

[16]  I D Kuntz,et al.  Potent, low-molecular-weight non-peptide inhibitors of malarial aspartyl protease plasmepsin II. , 1999, Journal of medicinal chemistry.

[17]  K. Dill.  Theory for the folding and stability of globular proteins. , 1985, Biochemistry.

[18]  S. Anderson,et al.  Binding of amino acid side-chains to S1 cavities of serine proteinases. , 1997, Journal of molecular biology.

[19]  S. Peyerimhoff.  Spectroscopy: Computational Methods , 2002 .

[20]  D. Agard,et al.  Conformational substates in enzyme mechanism: The 120 K structure of α‐lytic protease at 1.5 Å resolution , 1997, Protein science : a publication of the Protein Society.

[21]  Robin J. Wilson.  Introduction to Graph Theory , 1974 .

[22]  Walter Kauzmann,et al.  The Structure and Properties of Water , 1969 .

[23]  K. Dill,et al.  From Levinthal to pathways to funnels , 1997, Nature Structural Biology.

[24]  The choice of optimal parameters for measurement of spin-lattice relaxation times. III. Mathematical preliminaries for nonideal pulses , 1985 .

[25]  T. Halgren,et al.  A priori prediction of activity for HIV-1 protease inhibitors employing energy minimization in the active site. , 1995, Journal of medicinal chemistry.

[26]  A. Brunger.  Free R value: a novel statistical quantity for assessing the accuracy of crystal structures. , 1992 .

[27]  V. Helms.  Electronic excitations of biomolecules studied by quantum chemistry. , 2002, Current opinion in structural biology.

[28]  D J Diller,et al.  High throughput docking for library design and library prioritization , 2001, Proteins.

[29]  C. Lecomte.  Experimental electron densities of molecular crystals and calculation of electrostatic properties from high resolution X-ray diffraction , 1995 .

[30]  D C Spellmeyer,et al.  Measuring diversity: experimental design of combinatorial libraries for drug discovery. , 1995, Journal of medicinal chemistry.

[31]  R. Woody,et al.  The effect of conformation on the CD of interacting helices: A theoretical study of tropomyosin , 1990, Biopolymers.

[32]  R Leplae,et al.  Analysis and assessment of comparative modeling predictions in CASP4 , 2001, Proteins.

[33]  I. Kuntz,et al.  Inclusion of Solvation in Ligand Binding Free Energy Calculations Using the Generalized-Born Model , 1999 .

[34]  M. Karplus,et al.  Effective energy function for proteins in solution , 1999, Proteins.

[35]  C. Blouin,et al.  Probing electrostatic interactions in cytochrome c using site-directed chemical modification. , 2002, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[36]  V. Luzzati,et al.  Traitement statistique des erreurs dans la determination des structures cristallines , 1952 .

[37]  Dorothy Crowfoot Hodgkin,et al.  BIOMOLECULAR STRUCTURE, CONFORMATION, FUNCTION, AND EVOLUTION , 1981 .

[38]  C. Hansch.  Quantitative approach to biochemical structure-activity relationships , 1969 .

[39]  Michael W. Mahoney,et al.  Quantum, intramolecular flexibility, and polarizability effects on the reproduction of the density anomaly of liquid water by simple potential functions , 2001 .

[40]  P. Kollman,et al.  Molecular dynamics and binding specificity analysis of the bovine immunodeficiency virus BIV Tat-TAR complex. , 2001, Biophysical journal.

[41]  Piotr Cieplak,et al.  Molecular dynamics and free energy analyses of cathepsin D-inhibitor interactions: insight into structure-based ligand design. , 2002, Journal of medicinal chemistry.

[42]  J L Sussman,et al.  Protein Data Bank archives of three-dimensional macromolecular structures. , 1997, Methods in enzymology.

[43]  I D Kuntz,et al.  Structure-based identification of an inducer of the low-pH conformational change in the influenza virus hemagglutinin: irreversible inhibition of infectivity , 1997, Journal of virology.

[44]  Ken A. Dill,et al.  A Simple Model of Water and the Hydrophobic Effect , 1998 .

[45]  R J Read,et al.  Crystallography & NMR system: A new software suite for macromolecular structure determination. , 1998, Acta crystallographica. Section D, Biological crystallography.

[46]  E. Freire,et al.  Direct measurement of protein binding energetics by isothermal titration calorimetry. , 2001, Current Opinion in Structural Biology.

[47]  D. Case,et al.  Molecular Dynamics Simulations of Nucleic Acids with a Generalized Born Solvation Model , 2000 .

[48]  Huafeng Xu,et al.  A self-organizing principle for learning nonlinear manifolds , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[49]  W. L. Jorgensen,et al.  Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids , 1996 .

[50]  Ruhong Zhou,et al.  New Linear Interaction Method for Binding Affinity Calculations Using a Continuum Solvent Model , 2001 .

[51]  P. Kollman,et al.  A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules , 1995 .

[52]  A. Fersht,et al.  Protein Folding and Unfolding at Atomic Resolution , 2002, Cell.

[53]  A. Hagler,et al.  Theoretical studies of the structure and molecular dynamics of a peptide crystal. , 1988, Biochemistry.

[54]  M. Zalis,et al.  Visualizing and quantifying molecular goodness-of-fit: small-probe contact dots with explicit hydrogen atoms. , 1999, Journal of molecular biology.

[55]  K N Houk,et al.  Theozymes and compuzymes: theoretical models for biological catalysis. , 1998, Current opinion in chemical biology.

[56]  I D Kuntz,et al.  Structure-based design and combinatorial chemistry yield low nanomolar inhibitors of cathepsin D. , 1997, Chemistry & biology.

[57]  M. Zuker.  On finding all suboptimal foldings of an RNA molecule. , 1989, Science.

[58]  Y. Jan,et al.  Probing Protein Electrostatics with a Synthetic Fluorescent Amino Acid , 2002, Science.

[59]  K M Merz,et al.  New developments in applying quantum mechanics to proteins. , 2001, Current opinion in structural biology.

[60]  Arto Salomaa.  A Deterministic Algorithm for Modular Knapsack Problems , 1991, Theor. Comput. Sci..

[61]  I D Kuntz,et al.  Inhibitors of kinesin activity from structure-based computer screening. , 2000, Biochemistry.

[62]  Paul S. Charifson,et al.  Practical Application of Computer-Aided Drug Design , 1997 .

[63]  V. Pande,et al.  Absolute comparison of simulated and experimental protein-folding dynamics , 2002, Nature.

[64]  Chris Sander,et al.  Who checks the checkers? Four validation tools applied to eight atomic resolution structures. EU 3-D Validation Network. , 1998, Journal of molecular biology.

[65]  G. Sheldrick,et al.  SHELXL: high-resolution refinement. , 1997, Methods in enzymology.

[66]  S Wold,et al.  Multivariate data analysis and experimental design in biomedical research. , 1988, Progress in medicinal chemistry.

[67]  Amedeo Caflisch,et al.  Calculation of protein ionization equilibria with conformational sampling: pKa of a model leucine zipper, GCN4 and barnase , 2002, Proteins.

[68]  David A. Case,et al.  Effective Born radii in the generalized Born approximation: The importance of being perfect , 2002, J. Comput. Chem..

[69]  P. Schleyer.  Encyclopedia of computational chemistry , 1998 .

[70]  Timothy F. Havel.  Distance Geometry: Theory, Algorithms, and Chemical Applications , 2002 .

[71]  Junichi Higo,et al.  Hydration structure of human lysozyme investigated by molecular dynamics simulation and cryogenic X‐ray crystal structure analyses: On the correlation between crystal water sites, solvent density, and solvent dipole , 2002, J. Comput. Chem..

[72]  P. Kollman.  Advances and Continuing Challenges in Achieving Realistic and Predictive Simulations of the Properties of Organic and Biological Molecules , 1996 .

[73]  Irwin D Kuntz,et al.  Free energy calculations for theophylline binding to an RNA aptamer: Comparison of MM-PBSA and thermodynamic integration methods. , 2003, Biopolymers.

[74]  David C. Sullivan,et al.  Protein Folding as Biased Conformational Diffusion , 2002 .

[75]  D. Leckband,et al.  Intermolecular forces in biology , 2001, Quarterly Reviews of Biophysics.

[76]  K. Sharp,et al.  On the calculation of absolute macromolecular binding free energies , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[77]  S Wold,et al.  Chemometrics, why, what and where to next? , 1991, Journal of pharmaceutical and biomedical analysis.

[78]  X. Daura,et al.  Unfolded state of peptides. , 2002, Advances in protein chemistry.

[79]  G J Kleywegt,et al.  Experimental assessment of differences between related protein crystal structures. , 1999, Acta crystallographica. Section D, Biological crystallography.

[80]  X. Daura,et al.  Entropy calculations on a reversibly folding peptide: Changes in solute free energy cannot explain folding behavior , 2001, Proteins.

[81]  Malin M. Young,et al.  High throughput protein fold identification by using experimental constraints derived from intramolecular cross-links and mass spectrometry , 2000, Proc. Natl. Acad. Sci. USA.

[82]  G J Kleywegt,et al.  Validation of protein crystal structures. , 2000, Acta crystallographica. Section D, Biological crystallography.

[83]  P. Kollman,et al.  Pathways to a protein folding intermediate observed in a 1-microsecond simulation in aqueous solution. , 1998, Science.

[84]  Z. Xia,et al.  Effect of mutation at valine 61 on the three-dimensional structure, stability, and redox potential of cytochrome b5. , 1999, Biochemistry.

[85]  Michael K. Gilson,et al.  ''Mining minima'': Direct computation of conformational free energy , 1997 .

[86]  T. James,et al.  Determination of the populations and structures of multiple conformers in an ensemble from NMR data: Multiple-copy refinement of nucleic acid structures using floating weights , 2000, Journal of biomolecular NMR.

[87]  D. Case,et al.  Generalized born models of macromolecular solvation effects. , 2000, Annual review of physical chemistry.

[88]  P. Kollman,et al.  A well-behaved electrostatic potential-based method using charge restraints for deriving atomic char , 1993 .

[89]  Z. Xiang,et al.  On the role of the crystal environment in determining protein side-chain conformations. , 2002, Journal of molecular biology.

[90]  Niels Grønbech-Jensen,et al.  Highly constrained multiple‐copy refinement of protein crystal structures , 1997, Proteins.

[91]  W. Hendrickson,et al.  STEREOCHEMICALLY RESTRAINED CRYSTALLOGRAPHIC LEAST-SQUARES REFINEMENT OF MACROMOLECULE STRUCTURES , 1981 .

[92]  M. Nilges,et al.  Influence of non-bonded parameters on the quality of NMR structures: A new force field for NMR structure calculation , 1999, Journal of biomolecular NMR.

[93]  J. Pitera,et al.  Assessing the effect of conformational averaging on the measured values of observables , 2001, Journal of biomolecular NMR.

[94]  M. Mezei,et al.  Monte Carlo Computer Simulation Studies of the Equilibrium Properties and Structure of Liquid Water , 1983 .

[95]  R M Knegtel,et al.  Efficacy and selectivity in flexible database docking , 1999, Proteins.

[96]  X Chen,et al.  The binding database: overview and user's guide. , 2001, Biopolymers.

[97]  C L Brooks,et al.  Ligand-protein database: linking protein-ligand complex structures to binding data. , 2001, Journal of medicinal chemistry.

[98]  H Rabitz,et al.  Systems Analysis at the Molecular Scale , 1989, Science.

[99]  Lorna J. Smith,et al.  Assessing equilibration and convergence in biomolecular simulations , 2002, Proteins.

[100]  B. Honig,et al.  Classical electrostatics in biology and chemistry. , 1995, Science.

[101]  Michael Nilges,et al.  Molecular dynamics and accuracy of NMR structures: Effects of error bounds and data removal , 1999, Proteins.

[102]  P. Kollman,et al.  Binding of a diverse set of ligands to avidin and streptavidin: an accurate quantitative prediction of their relative affinities by a combination of molecular mechanics and continuum solvent models. , 2000, Journal of medicinal chemistry.

[103]  W. Eaton,et al.  Probing the free-energy surface for protein folding with single-molecule fluorescence spectroscopy , 2002, Nature.

[104]  S. Anderson,et al.  Predicting the reactivity of proteins from their sequence alone: Kazal family of protein inhibitors of serine proteinases. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[105]  K. Dill,et al.  Thermal stabilities of globular proteins. , 1989, Biochemistry.

[106]  A. Sali,et al.  Protein Structure Prediction and Structural Genomics , 2001, Science.

[107]  L. Wong,et al.  Surface‐modified mutants of cytochrome P450cam: enzymatic properties and electrochemistry , 1999, FEBS letters.

[108]  P. Kollman,et al.  Simulating proteins at constant pH: An approach combining molecular dynamics and Monte Carlo simulation , 2002, Proteins.

[109]  Richard Bonneau,et al.  Ab initio protein structure prediction: progress and prospects. , 2001, Annual review of biophysics and biomolecular structure.

[110]  E. R. Andrew,et al.  Nuclear Magnetic Resonance , 1955 .

[111]  R M Stroud,et al.  Significance of structural changes in proteins: Expected errors in refined protein structures , 1995, Protein science : a publication of the Protein Society.