Force computations in automated docking

Hypocrea jecorina (formerly Trichoderma reesei) Cel7A has a catalytic domain (CD) and a cellulose-binding domain (CBD) separated by a highly glycosylated linker. Very little is known of how the two domains interact to degrade crystalline cellulose. Based on the interaction energies and forces on cellooligosaccharides computationally docked to the CD and CBD, we propose a molecular machine model where the CBD wedges itself under a free chain end on the crystalline cellulose surface and feeds it to the CD active-site tunnel. Enzyme-substrate interactions produce the forces required to pull cellulose chains from the surface and also to help the enzyme move on the cellulose chain for processive hydrolysis. The energy to generate these forces is ultimately derived from the chemical energy of glyco­ side bond breakage. INTRODUCTION Cellulases are of two types: endoglucanases (EGs, EC 3.2.1.4), breaking internal bonds in amorphous cellulose chains to form cellooligosaccharides; and cellobiohydrolases (CBH's, EC 3.2.1.91), releasing cellobiose (Cel?) from cellooligosaccharide and crystalline cellulose chain ends. CBH I's cleave Celz from reducing ends, leaving {3-anomers, while CBHII's cleave a-Ceh from nonreducing ends. Based on sequence similarities, glycosyl hydrolases are classified into >90 families.1 Glycoside hydrolase Family 7 (GH7), whose members are almost all from ascomycotal and basidiomycotal fungi, contains CBH I's (Cel7A's) and

[1]  R N Goldberg,et al.  Thermodynamics of hydrolysis of disaccharides. Cellobiose, gentiobiose, isomaltose, and maltose. , 1989, The Journal of biological chemistry.

[2]  S. Flitsch,et al.  Enzyme-catalyzed formation of glycosidic linkages. , 1997, Current opinion in structural biology.

[3]  P. Howell,et al.  Mutation of Arg273 to Leu Alters the Specificity of the Yeast N-Glycan Processing Class I α1,2-Mannosidase* , 2000, The Journal of Biological Chemistry.

[4]  Hans-Joachim Böhm,et al.  LUDI: rule-based automatic design of new substituents for enzyme inhibitor leads , 1992, J. Comput. Aided Mol. Des..

[5]  P. Goodford.  A computational procedure for determining energetically favorable binding sites on biologically important macromolecules. , 1985, Journal of medicinal chemistry.

[6]  P. Kraulis,et al.  Investigation of the function of mutated cellulose‐binding domains of Trichoderma reesei cellobiohydrolase I , 1992, Proteins.

[7]  J. Bajorath,et al.  Docking and scoring in virtual screening for drug discovery: methods and applications , 2004, Nature Reviews Drug Discovery.

[8]  S. Ōmura,et al.  Novel Aspects of Degradation of T Cell Receptor Subunits from the Endoplasmic Reticulum (ER) in T Cells: Importance of Oligosaccharide Processing, Ubiquitination, and Proteasome-dependent Removal from ER Membranes , 1998, The Journal of experimental medicine.

[9]  Tirso Pons,et al.  Homology modeling, model and software evaluation: three related resources , 1998, Bioinform..

[10]  David S. Goodsell,et al.  Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function , 1998, J. Comput. Chem..

[11]  Aaron R. Dinner,et al.  Uracil-DNA glycosylase acts by substrate autocatalysis , 2001, Nature.

[12]  G J Davies,et al.  Structure of the Fusarium oxysporum endoglucanase I with a nonhydrolyzable substrate analogue: substrate distortion gives rise to the preferred axial orientation for the leaving group. , 1996, Biochemistry.

[13]  D. Perlmutter,et al.  Glucosidase and Mannosidase Inhibitors Mediate Increased Secretion of Mutant α1 Antitrypsin Z* , 2000, The Journal of Biological Chemistry.

[14]  Alain Laederach,et al.  Modeling protein recognition of carbohydrates , 2005, Proteins.

[15]  G. Klebe,et al.  Knowledge-based scoring function to predict protein-ligand interactions. , 2000, Journal of molecular biology.

[16]  P. Kollman,et al.  A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules J. Am. Chem. Soc. 1995, 117, 5179−5197 , 1996 .

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

[18]  M. Claeyssens,et al.  Structural and functional domains of cellobiohydrolase I from trichoderma reesei , 1988, European Biophysics Journal.

[19]  Norman L. Allinger,et al.  Molecular mechanics. The MM3 force field for hydrocarbons. 1 , 1989 .

[20]  W. Hart.  Adaptive global optimization with local search , 1994 .

[21]  Ruth Nussinov,et al.  Principles of docking: An overview of search algorithms and a guide to scoring functions , 2002, Proteins.

[22]  Peter J. Reilly,et al.  Modeling of aldopyranosyl ring puckering with MM3 (92) , 1994 .

[23]  John M. Stubbs,et al.  Glycosidic bond formation in aqueous solution: on the oxocarbenium intermediate. , 2003, Journal of the American Chemical Society.

[24]  A. Herscovics.  Processing glycosidases of Saccharomyces cerevisiae. , 1999, Biochimica et biophysica acta.

[25]  M. Claeyssens,et al.  Domain structure of cellobiohydrolase II as studied by small angle X-ray scattering: close resemblance to cellobiohydrolase I. , 1988, Biochemical and biophysical research communications.

[26]  M. Harris,et al.  Engineering the exo-loop of Trichoderma reesei cellobiohydrolase, Cel7A. A comparison with Phanerochaete chrysosporium Cel7D. , 2003, Journal of molecular biology.

[27]  A. Herscovics,et al.  Glycosidases of the asparagine-linked oligosaccharide processing pathway. , 1994, Glycobiology.

[28]  R Abagyan,et al.  Flexible protein–ligand docking by global energy optimization in internal coordinates , 1997, Proteins.

[29]  P. Coutinho,et al.  Automated docking of monosaccharide substrates and analogues and methyl α‐Acarviosinide in the glucoamylase active site , 1997, Proteins.

[30]  T. A. Jones,et al.  High-resolution crystal structures reveal how a cellulose chain is bound in the 50 A long tunnel of cellobiohydrolase I from Trichoderma reesei. , 1998, Journal of molecular biology.

[31]  C. Divne,et al.  Activity studies and crystal structures of catalytically deficient mutants of cellobiohydrolase I from Trichoderma reesei. , 1996, Journal of molecular biology.

[32]  D. Kilburn,et al.  Deletion of the linker connecting the catalytic and cellulose-binding domains of endoglucanase A (CenA) of Cellulomonas fimi alters its conformation and catalytic activity. , 1991, The Journal of biological chemistry.

[33]  B. Henrissat,et al.  Stereochemistry, specificity and kinetics of the hydrolysis of reduced cellodextrins by nine cellulases. , 1993, European journal of biochemistry.

[34]  M. Sinnott.  The cellobiohydrolases of Trichoderma reesei: a review of indirect and direct evidence that their function is not just glycosidic bond hydrolysis. , 1998, Biochemical Society transactions.

[35]  R. Atalla,et al.  Native Cellulose: A Composite of Two Distinct Crystalline Forms , 1984, Science.

[36]  R. Newman,et al.  Conformational features of crystal-surface cellulose from higher plants. , 2002, The Plant journal : for cell and molecular biology.

[37]  P. V. von Hippel,et al.  Helicase mechanisms and the coupling of helicases within macromolecular machines Part II: Integration of helicases into cellular processes , 2003, Quarterly Reviews of Biophysics.

[38]  A. Laederach,et al.  Arg343 in human surfactant protein D governs discrimination between glucose and N-acetylglucosamine ligands. , 2004, Glycobiology.

[39]  Thomas Lengauer,et al.  A fast flexible docking method using an incremental construction algorithm. , 1996, Journal of molecular biology.

[40]  P. Reilly,et al.  Understanding protein structure‐function relationships in Family 47 α‐1,2‐mannosidases through computational docking of ligands , 2002, Proteins.

[41]  T. Reinikainen,et al.  The three-dimensional crystal structure of the catalytic core of cellobiohydrolase I from Trichoderma reesei. , 1994, Science.

[42]  R. Newman.  Evidence for assignment of 13C NMR signals to cellulose crystallite surfaces in wood, pulp and isolated celluloses , 1998 .

[43]  M. Aebi,et al.  Degradation of Misfolded Endoplasmic Reticulum Glycoproteins in Saccharomyces cerevisiae Is Determined by a Specific Oligosaccharide Structure , 1998, The Journal of cell biology.

[44]  P Willett,et al.  Development and validation of a genetic algorithm for flexible docking. , 1997, Journal of molecular biology.

[45]  Stanislaw Bartkiewicz,et al.  Brownian motion, molecular motors and ratchets , 2004 .

[46]  H. Wolfson,et al.  Small molecule recognition: solid angles surface representation and molecular shape complementarity. , 1999, Combinatorial chemistry & high throughput screening.

[47]  D. van der Spoel,et al.  Efficient docking of peptides to proteins without prior knowledge of the binding site , 2002, Protein science : a publication of the Protein Society.

[48]  I. S. Pretorius,et al.  Microbial Cellulose Utilization: Fundamentals and Biotechnology , 2002, Microbiology and Molecular Biology Reviews.

[49]  Yan Liu,et al.  Oligosaccharide Modification in the Early Secretory Pathway Directs the Selection of a Misfolded Glycoprotein for Degradation by the Proteasome* , 1999, The Journal of Biological Chemistry.

[50]  D. Koshland,et al.  Prediction of the structure of a receptor–protein complex using a binary docking method , 1992, Nature.

[51]  Brian J. Smith.  A CONFORMATIONAL STUDY OF 2-OXANOL : INSIGHT INTO THE ROLE OF RING DISTORTION ON ENZYME-CATALYZED GLYCOSIDIC BOND CLEAVAGE , 1997 .

[52]  J. Sugiyama,et al.  Electron diffraction study on the two crystalline phases occurring in native cellulose from an algal cell wall , 1991 .

[53]  Roger J.-B. Wets,et al.  Minimization by Random Search Techniques , 1981, Math. Oper. Res..

[54]  B Honig,et al.  Computer simulations of the diffusion of a substrate to an active site of an enzyme. , 1987, Science.

[55]  P. Coutinho,et al.  Automated docking of isomaltose analogues in the glucoamylase active site , 1997 .

[56]  Guanjun Chen,et al.  Non-hydrolytic Disruption of Crystalline Structure of Cellulose by Cellulose Binding Domain and Linker Sequence of Cellobiohydrolase I from Penicillium janthinellum. , 2001, Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica.

[57]  L. Heux,et al.  Molecular Dynamics Simulations of Bulk Native Crystalline and Amorphous Structures of Cellulose , 2003 .

[58]  R. Glen,et al.  Molecular recognition of receptor sites using a genetic algorithm with a description of desolvation. , 1995, Journal of molecular biology.

[59]  M. Penttilä,et al.  Role of the interdomain linker peptide of Trichoderma reesei cellobiohydrolase I in its interaction with crystalline cellulose. , 1993, The Journal of biological chemistry.

[60]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[61]  A J Olson,et al.  Automated docking in crystallography: Analysis of the substrates of aconitase , 1993, Proteins.

[62]  J. Marth,et al.  Alpha-Mannosidase-II Deficiency Results in Dyserythropoiesis and Unveils an Alternate Pathway in Oligosaccharide Biosynthesis , 1997, Cell.

[63]  M. Linder,et al.  Widely different off rates of two closely related cellulose-binding domains from Trichoderma reesei. , 1999, European journal of biochemistry.

[64]  F. Tjerneld,et al.  Hydrolysis of microcrystalline cellulose by cellobiohydrolase I and endoglucanase II from Trichoderma reesei: adsorption, sugar production pattern, and synergism of the enzymes. , 1998, Biotechnology and bioengineering.

[65]  D. Kilburn,et al.  C1-Cx revisited: intramolecular synergism in a cellulase. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[66]  A. Laederach,et al.  Automated docking of maltose, 2‐deoxymaltose, and maltotetraose into the soybean β‐amylase active site , 1999, Proteins.

[67]  R. M. Burnett,et al.  DARWIN: A program for docking flexible molecules , 2000, Proteins.

[68]  A. Leach,et al.  Ligand docking to proteins with discrete side-chain flexibility. , 1994, Journal of molecular biology.

[69]  Peter Novick,et al.  Guidebook to the secretory pathway , 1994 .

[70]  I. Kuntz,et al.  Molecular docking to ensembles of protein structures. , 1997, Journal of molecular biology.

[71]  J. Ståhlberg,et al.  A New Model For Enzymatic Hydrolysis of Cellulose Based on the Two-Domain Structure of Cellobiohydrolase I , 1991, Bio/Technology.

[72]  M. Androlewicz,et al.  Oligosaccharide trimming plays a role in the endoplasmic reticulum-associated degradation of tyrosinase. , 2000, Biochemical and biophysical research communications.

[73]  A. Annila,et al.  Identification of functionally important amino acids in the cellulose‐binding domain of Trichoderma reesei cellobiohydrolase I , 1995, Protein science : a publication of the Protein Society.

[74]  B. Henrissat,et al.  Structures and mechanisms of glycosyl hydrolases. , 1995, Structure.

[75]  J A McCammon,et al.  Accommodating protein flexibility in computational drug design. , 2000, Molecular pharmacology.

[76]  A. Seymour,et al.  Meaning of energetic parameters , 1993, Basic Research in Cardiology.

[77]  Ruben Abagyan,et al.  Comparative study of several algorithms for flexible ligand docking , 2003, J. Comput. Aided Mol. Des..

[78]  Daniel E. Koshland,et al.  STEREOCHEMISTRY AND THE MECHANISM OF ENZYMATIC REACTIONS , 1953 .

[79]  M. L. Connolly.  Analytical molecular surface calculation , 1983 .

[80]  A. Koivula,et al.  Cellulose-binding domains promote hydrolysis of different sites on crystalline cellulose. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[81]  W. Steiner,et al.  Cellulose hydrolysis by the cellulases from Trichoderma reesei: adsorptions of two cellobiohydrolases, two endocellulases and their core proteins on filter paper and their relation to hydrolysis. , 1994, The Biochemical journal.

[82]  J. Sugiyama,et al.  New insight into cellulose structure by atomic force microscopy shows the i(alpha) crystal phase at near-atomic resolution. , 2000, Biophysical journal.

[83]  Thomas Simonson,et al.  Free energy simulations come of age: protein-ligand recognition. , 2002, Accounts of chemical research.

[84]  Zachary Shriver,et al.  Glycomics: a pathway to a class of new and improved therapeutics , 2004, Nature Reviews Drug Discovery.

[85]  W. Hintz,et al.  Characterization of the Class I α-mannosidase gene family in the filamentous fungus Aspergillus nidulans , 2000 .

[86]  P. Bonay,et al.  Characterization of a mannosidase acting on α1 → 3‐ and α1 → 6‐linked mannose residues of oligomannosidic intermediates of glycoprotein processing , 1987 .

[87]  G J Davies,et al.  Nomenclature for sugar-binding subsites in glycosyl hydrolases. , 1997, The Biochemical journal.

[88]  Chandrika Mulakala,et al.  Force calculations in automated docking: Enzyme–substrate interactions in Fusarium oxysporum Cel7B , 2005, Proteins.

[89]  B Henrissat,et al.  A classification of glycosyl hydrolases based on amino acid sequence similarities. , 1991, The Biochemical journal.

[90]  David S. Goodsell,et al.  Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function , 1998 .

[91]  M. L. Connolly.  Solvent-accessible surfaces of proteins and nucleic acids. , 1983, Science.

[92]  M. Claeyssens,et al.  A hydrophobic platform as a mechanistically relevant transition state stabilising factor appears to be present in the active centre of all glycoside hydrolases , 2003, FEBS letters.

[93]  Peter A. Kollman,et al.  FREE ENERGY CALCULATIONS : APPLICATIONS TO CHEMICAL AND BIOCHEMICAL PHENOMENA , 1993 .

[94]  P. Coutinho,et al.  Automated docking of glucosyl disaccharides in the glucoamylase active site , 1997, Proteins.

[95]  S. Kornfeld,et al.  Assembly of asparagine-linked oligosaccharides. , 1985, Annual review of biochemistry.

[96]  R. Newman,et al.  Molecular conformations at the cellulose–water interface , 2004 .

[97]  B. Evans,et al.  The mechanism of cellulase action on cotton fibers: evidence from atomic force microscopy. , 2000, Ultramicroscopy.

[98]  Tuula T. Teeri,et al.  The roles and function of cellulose-binding domains , 1997 .

[99]  A. Annila,et al.  Solution structure of the cellulose-binding domain of endoglucanase I from Trichoderma reesei and its interaction with cello-oligosaccharides. , 1998, European journal of biochemistry.

[100]  A. Laederach,et al.  Polysaccharide recognition by surfactant protein D: novel interactions of a C-type lectin with nonterminal glucosyl residues. , 2001, Biochemistry.

[101]  Todd J. A. Ewing,et al.  DOCK 4.0: Search strategies for automated molecular docking of flexible molecule databases , 2001, J. Comput. Aided Mol. Des..

[102]  P. Kraulis,et al.  Determination of the three-dimensional solution structure of the C-terminal domain of cellobiohydrolase I from Trichoderma reesei. A study using nuclear magnetic resonance and hybrid distance geometry-dynamical simulated annealing. , 1989, Biochemistry.

[103]  A. Annila,et al.  Three‐dimensional structures of three engineered cellulose‐binding domains of cellobiohydrolase I from Trichoderma reesei , 1997, Protein science : a publication of the Protein Society.

[104]  C. Haynes,et al.  Surface Diffusion of Cellulases and Their Isolated Binding Domains on Cellulose* , 1997, The Journal of Biological Chemistry.

[105]  N. Vyas.  Atomic features of protein-carbohydrate interactions , 1991 .

[106]  Wolfram Tempel,et al.  Mechanism of Class 1 (Glycosylhydrolase Family 47) α-Mannosidases Involved in N-Glycan Processing and Endoplasmic Reticulum Quality Control* , 2005, Journal of Biological Chemistry.