黃鎮剛 教授  國立交通大學 生物科技學院院長  生物資訊研究所  Professor Jenn-Kang Hwang  Dean, College of Biol. Sci. & Tech.  Institute of Bioinformatics  National Chiao Tung University, HsinChu, Taiwan  E-mail: jkhwang (at) cc . nctu . edu . tw  Tel : +886-3-513-1337  Fax: +886-572-9288  Research Topics Structure prediction and classification Prediction of protein subcellular localization Disulfide proteins Protein stability Structural alignment Molecular Simulation Sequence coupling Whatever is fun  Academic activities Editorial Board of Proteins: Structure, Function and Bioinformatics Editorial Board of Recent Patents on Anti-Infective Drug Discovery Editorial Board of the International Journal of Medical Engineering and Informatics President of Bioinformatics Society Taiwan Director of the Center for Interdisciplinary Biological Science Research at NCTU Member of Biophysics Society of R.O.C. Radio Plot of B-factors (red) and the sequare of centroid distance (black) of 1U0S Protein subcellular localization   Due to recent progress in genomics research, incredible amounts of DNA and protein sequence data are generated in great speed from experiment. Hence, to develop useful computational tools to extract relevant biological information from sequences becomes even more important nowadays. Due to the close correlation between the subcellular location of a protein and its biological function, the knowledge of subcellular location can help to characterize the protein functions. Therefore, a reliable, automated prediction tool for subcellular localization will be useful for the characterization of expressed protein sequences. We have developed a method CELLO based on Sopport Vector Machine to predict the subcellular locations for both eukaryotes and prokaryotes. See Nature Review Microbiology for a review of CELLO Structural entropy and thermostability We developed a technique to compute the structural entropy directly from protein sequences. We explored the possibility of using structural entropy to identify residues involved in thermal stabilization of various protein families. We observed a good linear relationship between the average structural entropy and the melting temperatures for adenylate kinase and its chimeric constructs. Structural alignment   Identify functional structural motifs from structures of unknown function becomes increasingly important in recent years due to the progress of the structural genomics projects. Though some structural patterns such as the Asp-His-Ser catalytic triad are easy to detect because of their conserved residues and the stringently constrained geometry, it is usually more challenging to detect a general structural motifs like, for example, ββα-metal binding motif, which has a much more variable conformation and sequence. At present, the identification of these motifs usually replies on manual procedures based on different structure and sequence analysis tools. We have developed a structural alignment algorithm combining both structural and sequence information to identify the local structure motifs. Molecular Simulation Understanding the molecular origin of enzyme catalysis is one of the most fundamental problems in molecular biology. The effects of enzymes on the reacting substrates involve varied and complicated energy contributions which depend on the structure of the enzyme-substrate complex. Thus to have a quantitative structure-function relationship is not a trivial matter. In principle, one would like to carry out ab initio quantum mechanical calculations for biomolecules. Unfortunately, such an approach cannot be implemented at present in studies of proteins. One must therefore resort to some approximations and represent a large part of the system classically. The enzymatic reactions are described by the empirical valence bond (EVB) method, which is probably one of the most practical and consistent approaches for treating chemical reactions both in enzymes and in solution. The basic idea is to represent the overall reaction in terms of various valence bond structures and then to obtain the actual ground state by mixing these structures. The EVB potential surface is calibrated by using accurate gas-phase data or by using experimental information for the corresponding reactions in solution. QM/MM simulation using Feynman's quantum beads In combination with the free energy perturbation (FEP) method, the EVB-FEP method offers a convenient way to calculate the free energy profile for the enzymatic reactions. We have carried out many EVB-FEP calculations on enzymes such as serine proteinases, aspartate aminotransferase and human carbonic anhydrase I. Recently, we have proposed the quantized classical path (QCP) approach which incorporates the Feynman's path integral into the EVB framework, and offers a convenient way to obtain quantum-mechanical corrections to the rate constants of proton transfer (PT) and hydride transfer reactions in enzymes and in solution. Efforts are also invested in combining the semi-empirical quantum mechanical method such as AM1 with the EVB- FEP approach. There is an interesting article in Nature reporting the recent progress in the study of QM effects on enzyme reactions and our related work.

Links   The Molecular Bioinformatics Center CELLO (PS)2 RCSB PDB SCOP NCBI The Structural Genomics Consortium Protein interaction domains nrpdb PDP Nature Science Nature: Structural & Molecular Biology Nature: Biotechnology Nature: Medicine Structure Current Opinion in Structural Biology Cell EMBO PNAS Genome Research Nucleic Acids Research Journal of Molecular Biology Protein Science Proteins: Structure, Function, and Bioinformatics Journal of American Chemical Society Accounts of Chemical Research Recent Patents on Anti-Infective Drug Discovery COMICS and OTHER FUN STUFF Rice University Anderson Auth Dilbert Carlson Oliphant Bok Sargent Doonsbury Garfield Bob's songs Poe Maimonides Chinese etymology Art Renewal Kitvei HaKodesh Jewish Humor 典籍 (Chinese) 韓非子 (Chinese) 慎子 (Chinese) 夢溪筆談 (Chinese) 西遊記 (Chinese) 三國演義 (Chinese) 颮翭 (Chinese)

Publications Huang SW, Shih CH, Lin CP, Hwang JK. Prediction of NMR order parameters in proteins using weighted protein contact-number model. Theor Chem Account, DOI 10.1007/s00214-008-0465-0. Lin et al. Deriving protein dynamical properties from weighted protein contact number, Proteins: Structure, Function and Bioinformatics [Accepted] Lu et al. On the relationship between the protein structure and protein dynamics, Proteins: Structure, Function and Bioinformatics [Accepted] Shih CH, Huang SW, Yen SC, Lai YL, Yu SH, Hwang JK. Computation of protein dynamics without a mechanical model, Proteins: Structure, Function and Bioinformatics (2007) 68, 34-38 Chiu, YY, Hwang JK, Yang JM, Soft energy function and generic evolutionary method for discriminating native from non-native protein conformations, J. Comp. Chem. [Accepted] Tsai YC, Lin YM, Hwang JK, Yu JSK, On the Stereochemistry of Zn-Zn Bonds: Synthesis, Structural Transformation, and Computations, Chem. Comm. (2007) 40:4125-4127 Su ECY, Chiu HS, Lo A, Hwang JK, TY Sung, WL Hsu, Protein subcellular localization prediction based on compartment-specific features and structure conservation, BMC Bioinformatics (2007) 8:330-341. Lai YL, Yen SC, Yu SH, Hwang JK. pKNOT: the Protein KNOT web server, Nucleic Acids Research (2007) 35:W420-W424 ; [Go to: The pKNOT server]. Wong YH, Lee TY, Liang HK, Huang CM, Yang YH, Chu CH, Huang HD, Ko MT, Hwang JK, KinasePhos 2.0: a web server for identifying protein kinase-specific phosphorylation sites based on sequences and coupling patterns, Nucleic Acids Research (2007) 35:W588-594. Huang CL, Liu JH, Chiu WC, Huang SW, Hwang JK, Wang WC. Crystal structure of Helicobacter pylori formamidase AmiF reveals a cysteine-glutamate-lysine catalytic triad. J. Biol. Chem. (2007) 282:12220-12229. Lin YS, Hsu WL, Hwang JK, Li WH. Proportion of solvent-exposed amino acids in a protein and rate of protein evolution, Molecular Biology and Evolution (2007) 24, 1005-11. Lu CH, Chen YC, Yu CS, Hwang JK. Predicting disulfide connectivity patterns, Proteins: Structure, Function and Bioinformatics (2007) 67: 262-270 Tsai YC, Lin YM, Yu, JSK, Hwang JK. A three-coordinate and quaruply bonded Mo-Mo-Complex, J. Am. Chem. Soc. (2006) 128:13980-13981 Lin YS, Byrnes JK, Hwang JK, Li WH. Codon usage bias versus gene conversion in the evolution of yeast duplicate genes. Proc. Natl. Acad. Sci. USA. (2006) 103:14412-14416 Lin YS, Hwang JK, Li WH. Protein complexity, gene duplicability and gene dispensability in the yeast genome. Gene. (2006) 387, 109-117. Yu CH, Chen YC, Lu CH, Hwang JK. Prediction of protein subcellular localization. Proteins: Sturcture, Function and Bioinformatics (2006), 64, 643-651 Chiu WC, You JY, Liu JS, Hsu SK, Hsu WH, Shih CH, Hwang JK, Wang WC, Structure-stability-activity relationship in covalently c 1 ross-linked N-carbamoyl D-amino acid amidohydrolase and N-acylamino acid racemase. J. Mol. Biol. (2006), 359: 741-753. Chen CC, Hwang JK, JM Yang. Protein structure prediction server. Nucleic Acid Research (2006), 34: W152-157. [Go to: (PS)2 server] Lu CH, Lin SH, Chen YC, Yu CS, Chang SY, Hwang JK. The fragment transformation method to detect the protein structural motifs. Proteins: Sturcture, Function and Bioinformatics (2006), 63:636-643. Hung SW, Hwang JK, Tseng F, Chang JM Chen CC, Chieng CC. Molecular dynamics simulation on enhancement of CTX and E6 protein binding on mixed SAMs molecules. Nanotechnology (2006), 17, S8-13 Chen YC, Hwang JK Prediction of disulfide connectivity from protein sequences. Proteins: Structure, Function and Bioinformatics (2005) 61, 507-512 . Huang SW, Hwang JK. Computation of conformational entropy from protein sequences using the machine-learning method – Application to the study of the relationship between structural conservation and local structural stability. Proteins: Structure, Function and Bioinformatics (2005), 59, 802-809. Liang HK, Huang CM, Ko MT, Hwang JK. The Amino Acid-Coupling Patterns in Thermophilic Proteins. Proteins: Structure, Function and Bioinformatics (2005), 59, 58-63. Lin YS, Tzeng CS, Hwang JK. Reassessment of morphological characters in freshwater eels (genus Anguilla, Anguillidae) shows congruence with molecular phylogeny estimate. Zoologica Scripta (2005), 34, 225-234. Chan CC, Liang HK, Hsiao NW, Ko MT, Lyu PC, Hwang JK. The relationship between local structural entropy and protein thermostability. Proteins: Structure, Function and Bioinformatics (2004) 57, 684-691. Chen YC, Lin YS, Lin CJ and Hwang JK. Prediction of the Bonding States of Cysteines using the Support Vector Machines Based on Multiple Feature Vectors and Cysteine State Sequences. Proteins: Structure, Function and Bioinformatics (2004), 55, 1046-42. Yu CS, Lin CJ, Hwang JK, Predicting Subcellular Localization of Proteins For Gram-Negative Bacteria by Support Vector Machines Based on n-Peptide Compositions. Protein Science (2004), 13, 1402-1406 Yu JSK, Hwang JK, Tang CY, Yu CH. Numerical performance and throughput benchmark for electronic structure calculations in PC-Linux System with new architectures, updated compilers and library. J. Chem. Inf. Comput. Sci (2004), 44, 635-642. Yu CS, Wang JY, Yang JM, Lyu PC, Lin CJ, Hwang JK, Fine-grained protein fold assignment by support vector machines using generalized n-peptide coding schemes and jury voting from multiple parameter sets. Proteins: Structure, Function and Genetics. (2003) 50, 531-536. C-C. Chuang, C-Y Chen, J.-M. Yang, P.-C. Lyu, J.-K. Hwang, Relationship between protein structures and disulfide-bonding patterns. Proteins: Structure, Function and Genetics (2003), 53, 1-5. J.-T. Horng, H.-D. Huang, S.-H. Wang, M.-Y. Chen, and J.-K. Hwang, Computing motif correlations in proteins. J. Comp. Chem. (2003), 24, 2032-2043. C. C. Chan, P. C. Lyu, J.-K. Hwang, Computation of the Protein Structure Entropy and its Applications to Protein Folding Processes. J. Chin. Chem. Soc. (2003), 50, 677-684. J.-M. Yang, C.-H. Tsai, M.-J. Hwang, H.-K. Tsai, J.-K. Hwang, C.-Y. Kao, GEM: A Gaussian evolutionary method for predicting protein side-chain conformations. Protein Sci. (2002), 11, 1897-1907. J.-K. Hwang, The Partial Averaging Fourier path integral approach based on the harmonic reference path. Theo. Chem. Acc.101 , 359-363 (1999) Z. Z. Fan, J.-K. Hwang, A. Warshel: Using simplified protein representation as a reference potential for all-atom calculations of folding free energy Theor Chem Acc 103 (1999) 1, 77-80 C.H. Lin, F.C.H. Chan, J.K. Hwang and P.C. Lyu, Calcium binding mode of -carboxyglutamic acids in conantokins Protein Engineering 12, 589-595, (1999) J.-K. Hwang, Calculation of Quantum Mechanical free energy at low temperature. Theo. Chem. Acc. 98, 202-205 (1998). A. A. Vyas, J.-J. Pan, H. V. Patel, K. A. Vyas, C.-M. Chiang, Y.-C. Sheu, J.-K. Hwang, W.-g. Wu, Analysis of binding of cobra cardiotoxins to heparin reveals a new beta-sheet heparin-binding structural motif. J. Biol. Chem. 272, 9661(1997) J.-K. Hwang & A. Warshel, On the relationship between the dispersed polaron and spin-boson models. Chem. Phys. Lett. 271, 223-225 (1997). J.-K. Hwang & A. Warshel, How important are quantum mechanical nuclear motions in enzyme catalysis. J. Am. Chem. Soc. 118, 11745 (1996).  J.-K. Hwang & J.-J. Pan, A Classical Trajectory Mapping Approach for Simulations of Chemical Reactions in Solution and in Enzymes. J. Phys. Chem. 100, 909 (1996) J.-J. Pan & J.-K. Hwang, Mixed Quantum Mechanical/Molecular Mechanical Simulations of Chemical Reactions in Solution and in Enzymes, in Biocomputing '96, edited by Lawrence Hunter and Teri E. Klein. (World Scientific, Singapore, 1996) p.539-549. J.-K. Hwang & J.-J. Pan, Simulation of Chemical Reactions in Solution by a Combination of Chemical and Quantum Mechanical Approach. Chem. Phys. Lett. 243, 171-175 (1995). J.-K. Hwang & W.-F. Liao, Side-chain prediction by neural networks and simulated annealing optimization. Protein Eng., 8, 363-370 (1995). J.-K. Hwang & A. Warshel, A Quantized Classical Path Approach for Calculations of Quantum Mechanical Rate Constants. J. Phys. Chem. 97, 10053-10058 (1993) . A. Warshel, J.-K. Hwang and J. Åqvist, Computer Simulations of Enzymatic reactions: Examination of Linear Free-Energy Relationships and Quantum-mechanical Corrections in the Initial Proton-Transfer Step of Carbonic Anhydrase. Faraday Discuss. 93, 225-238 (1992). J-K. Hwang, Z. T. Chu, A. Yadav and A. Warshel, Simulations of Quantum Mechanical Corrections for Rate Constants of Hydride-transfer Reactions in Enzymes and Solutions. J. Phys. Chem. 95 8445 (1991). A. Warshel, G. Naray-Szabo, F. Sussman & J-K. Hwang, in Perspectives in Biochemitsry Vol II, edited by Hans Neurath, (American Chemical Society , p. 115 (1991). A. Warshel, Z. T. Chu & J-K. Hwang, The Dynamics of the Primary event in rhodopsins revisted. Chem. Phys. 158 303 (1991). A. Warshel, G. Naray-Szabo, F. Sussman & J-K. Hwang, How Do Serine Proteases Really Work? Biochemistry 28 3629 (1989). J-K. Hwang and A. Warshel, Why Ion Pair Reversal by Protein Engineering is Unlikely to Succeed. Nature, 334 270 (1988). A. Warshel, F. Sussman and J-K. Hwang, Evaluation of Catalytic Free Energies in Genetically Modified Proteins. J. Mol. Biol. 201 139 (1988). S. Creighton, J-K Hwang, A. Warshel, W. W. Parson and J. Norris, Simulating The Dynamics of the Primary Charge Separation Process in Bacterial Photosynthesis. Biochemistry 27 774 (1988). J-K Hwang, S. Creighton, G. King, D. Whitney, and A. Warshel, Effects of Solute-Solvent Coupling and Solvent Saturation on Solvation Dynamics of Charge Transfer Reactions. J. Chem. Phys. 89 859 (1988). J-K Hwang, F. Sussman, and A.Warshel, Simulating the Energetics and Dynamics of Enzymatic Reactions in Genetically Modified Enzymes. in Structure and Expression, edited by R.H Sarma and M.H. Sarma (Adenine Press,New York 1988), p. 95. J-K Hwang, G. King, S. Creighton and A. Warshel, Simulation of Free Energy Relationships and Dynamics of SN2 Reactions in Aqueous Solutions. J. Am. Chem. Soc. 110 5297 (1988). J.-K. Hwang & A. Warshel, Semiquantitative Calculations of Catalytic Free energies in Genetically Modified Subtilisin. Biochemistry, 26, 2669 (1987). J.-K. Hwang & A. Warshel, Microscopic Examination of Free-Energy Relationships for Electron Transfer in Polar Solvents. J. Am. Chem. Soc. 109, 715 (1987). A. Warshel & J.-K. Hwang, Simulation of the Dynamics of Electron Transfer Reactions in Polar Solvents: Semiclassical Trajectories and Dispersed Polaron Approaches. J. Chem. Phys. 84, 4938 (1986). A. Warshel & J.-K. Hwang, Quantized Semiclassical Trajectory Approach for Evaluation of Vibronic Transitions in Anharmonic Molecules. J. Chem. Phys. 82, 1756(1985). J.-K. Hwang & A. Warshel, Semiclassical Simulation of the Spectra of Anharmonic Molecules: Problems and Alternatives. Chem. Phys. Lett. 115, 182 (1985). J.-K. Hwang & A. Warshel, A Shortcut for Multidimensional Quantization. The Average Partial Action Method. Chem. Phys. Lett. 118, 289 (1985). J.-K. Hwang, G.-C. Yen & L. S. Hwang, Detection of Vegetable Oil Adulteration by HPLC Analysis of Triglycerides. J. Chin. Agric. Chem. Soc. 91, 20 (1982).

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