STRUCTURE BASED PREDICTION OF CONFORMATIONAL & BINDING FREE ENERGIES
Barry H Honig, Professor
Institution:
Grant 5P41RR006009-070143 from National Center For Research Resources
Abstract: The goal of the research described in this proposal is the calculation to conformational free energies and binding free energies relevant to the structure and function of biological macromolecules. The specific problems of interest include the indentification of stable protein folds, the binding of drugs to the HIV protease and to the minor groove of DNA, and the binding of peptides and proteins to the surface of membranes. The overall strategy is to use molecular dynamics calculations to generate stable conformations, to evaluate their gas phase energies using molecular mechanics force fields, and to evaluate solvation free energies using continuum solvent models. The sum of the gas phase and solvation free energies yield conformational and binding free energies. The request is for sufficient computer time to carry out production runs on the specific problems of interest.
Sponsored Links Excellgen http://Excellgen.com
HIV: STRUCTURE BASED PREDICTION OF CONFORMATIONAL & BINDING FREE ENERGIES
Barry H Honig, Professor
Mellon Pitts Corporation (mpc Corp) Pittsburgh, Pa 152133890
Grant 5P41RR006009-130101 from National Center For Research Resources
Keywords: biological product, biomedical resource, computer
Project start date: 2002-08-01
Project end date: 2003-07-31
4 MONTH BIOMED GRANT LETTER WAS SENT TO D DEERFIELD
Barry H Honig, Professor
Mellon Pitts Corporation (mpc Corp) Pittsburgh, Pa 152133890
Grant 5P41RR006009-130199 from National Center For Research Resources
Project start date: 2002-08-01
Project end date: 2003-07-31
HIV: STRUCTURE BASED PREDICTION OF CONFORMATIONAL & BINDING FREE ENERGIES
Barry H Honig, Professor
Mellon Pitts Corporation (mpc Corp) Pittsburgh, Pa 152133890
Grant 5P41RR006009-120101 from National Center For Research Resources
Keywords: biological product, biomedical resource, computer
Project start date: 2001-08-01
Project end date: 2002-07-31
4 MONTH BIOMED GRANT LETTER WAS SENT TO D DEERFIELD
Barry H Honig, Professor
Mellon Pitts Corporation (mpc Corp) Pittsburgh, Pa 152133890
Grant 5P41RR006009-120199 from National Center For Research Resources
Project start date: 2001-08-01
Project end date: 2002-07-31
HIV: STRUCTURE BASED PREDICTION OF CONFORMATIONAL & BINDING FREE ENERGIES
Barry H Honig, Professor
Mellon Pitts Corporation (mpc Corp) Pittsburgh, Pa 152133890
Grant 5P41RR006009-100101 from National Center For Research Resources
Keywords: biological product, biomedical resource, computer
Project start date: 1999-08-01
Project end date: 2000-07-31
4 MONTH BIOMED GRANT LETTER WAS SENT TO D DEERFIELD
Barry H Honig, Professor
Institution:
Grant 5P41RR006009-100199 from National Center For Research Resources
Project start date: 1999-08-01
Project end date: 2000-07-31
STRUCT BASED PREDICTION OF CONFORMATIONAL & BINDING FREE ENERGIES: HIV PROTEASE
Barry H Honig, Professor
Mellon Pitts Corporation (mpc Corp) Pittsburgh, Pa 152133890
Grant 5P41RR006009-080127 from National Center For Research Resources
Keywords: AIDS, biological product, biomedical resource, communicable disease, immunology, lymphatic system, mineral, nucleic acid, protein, statistics /biometry, technology /technique development, virus
Project start date: 1997-09-01
Project end date: 1998-08-31
ELECTROSTATIC COMPUTATION OF PROTEIN INTERACTIONS NIH COLLABORATION
Barry H Honig
Mellon Pitts Corporation (mpc Corp) Pittsburgh, Pa 152133890
Grant 5P41RR006009-070066 from National Center For Research Resources
Grants awarded to Barry H Honig
BINDING AFFINITIES OF HIV ASPARTYL PROTEASE INHIBITORS
Barry H Honig, Professor
Columbia Univ New York Morningside Research Administration New York, Ny 100277003
Grant 5P41RR006892-100010 from National Center For Research Resources
Abstract: Wearetryingtocalculatetherelativebinding-freeenergiesof various drugs to the HIV aspartyl protease. We have chosen a series of closely related compounds for which both high resolution x-ray structures and binding affinities are available. Preliminary results utilize a continuum solvation model and the OPLS-AA force field of Jorgensen and coworkers are highly encouraging. A. Scientific Subproject
Keywords: AIDS, biological product, biomedical resource, computer, immunology, infection, inflammation, lymphatic system, protein, statistics /biometry, technology /technique, virus
Project start date: 2000-05-05
Project end date: 2002-04-30
Center For Computational Biology And Bioinformatics
Barry H Honig, Professor
Biochem & Molecular Biophysicscolumbia University Health Sciences
columbia University Medical Center
new York, Ny 100323702
Grant 1P20LM007276-01 from National Library Of Medicine IRG: ZRG1
Abstract: We propose to establish a Center for Computational Biology and Bioinformatics that will serve as a focal point for research and education at Columbia. The center will facilitate the integration of computational methods into different areas of biomedical research through the fostering of collaborations between laboratory and computational scientists, through training programs, workshops and seminars, and by providing the computational infrastructure and support that is necessary for cutting-edge research in this area. In-house research will include areas such as DNA and protein sequence analysis, SNP analysis and its relationship to human disease, protein structure analysis, the analysis of microarrays, the analysis and comparison of complete genomes, functional annotation of proteins, the study of networks of interacting proteins, and the 3D structure-based design of new pharmaceuticals. The center will play a central role in education through the development of joint courses and degree programs with participating departments. An industrial outreach program will also be established in which industrial scientists will be able to attend center lectures, symposia and workshops, spend mini-sabbaticals at the center, and establish research contacts with center scientists
Project start date: 2001-09-30
Project end date: 2004-08-31
1P20LM007276-01 (2001): $701157
BINDING AFFINITIES OF PROTEASE INHIBITORS: HIV ASPARTYL PROTEASE
Barry H Honig, Professor
Institution:
Grant 2P41RR006892-060009 from National Center For Research Resources
Abstract: We are trying to calculate the relative binding-free energies of various drugs to the HIV aspartyl protease. We have chosen a series of closely related compounds for which both high resolution x-ray structures and binding affinities are available. We have found that uncertainties in the crystal coordinates can have significant effects on the calculations leading to large differences in the calculated binding energies for drugs that are very similar. We are considering a number of approaches to deal with this problem including MD simulations so as to allow the x-ray coordinated to relax.
IMPLEMENTATION OF DELPHI ON MASSIVELY PARALLEL CM 5 SUPERCOMPUTER
Barry H Honig, Professor
Institution:
Grant 2P41RR006892-060012 from National Center For Research Resources
Abstract: We are porting DELPHI, a finite difference Poisson-Boltzmann solver developed in the Honig group, to the massively parallel CM-5 supercomputer. The CM-5 data parallel mode is very convenient for implementing the finite difference iterative algorithm in DELPHI and we expect to be able to obtain solutions for proteins on very dense grids in very short CPU times (on the order of seconds for 2563grids).
ELECTROSTATIC INTERACTIONS IN DNA
Barry H Honig, Professor
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 5R01GM041371-13 from National Institute Of General Medical Sciences IRG: BBCA
Abstract: Understanding the principles of DNA recognition by proteins and ligands is of central importance in biology and is directly relevant to a large body of problems associated with human disease. Similarly, RNA folding has become a problem of widespread interest, due to its relationship to fundamental biological processes and to new therapeutic approaches. The long range goal of the research described in the proposal is a detailed understanding of the relationships between structure and free energy that govern the structure and function of nucleic acids and their binding to various ligands and proteins. The specific goals of the proposed research are to study the large body of relevant structural and thermodynamic data that has accumulated in the past few years, and to use theoretical and computational methods to relate both types of measurements. For the DNA binding problem, a database of ligand and protein/DNA interfaces will be created. The GRASP program will be used to characterize the physical properties of the interfaces between ligand or proteins and DNA in complexes whose structures have been determined. Continuum methods will be used to calculate the binding free energies of the various complexes. In each case, the free energy will be partitioned into components with the goal of determining the major thermodynamic driving forces for the association of DNA with various ligands and proteins. Based on the accumulated data on structural parameters, calculated free energies and thermodynamic measurements, an attempt will be made to arrive at empirical rules that relate structure to free energy in DNA association reactions. For the RNA folding problem, Poisson-Boltzmann calculations will be used to describe the ion atmosphere and electrostatic potentials around all RNA molecules whose structures are known. These will then be related to measurements of the salt dependence of RNA conformational change. The electrostatic potentials will also be used as basis for understanding the large pKa shifts for some bases that have been observed in ribozymes. Continuum methods will be used to calculate and partition conformational free energies associated with the formation of RNA tertiary structure.
Keywords: bioenergetics, chemical structure /function, ionic bond, nucleic acid structure, protein folding, ribozyme, thermodynamics, DNA binding protein, RNA, active site, chemical information system, conformation, electrical potential, mathematical model, statistics /biometry
Project start date: 1988-12-01
Project end date: 2001-11-30
5R01GM041371-13 (2001): $132024
5R01GM041371-12 (2000): $170395
5R01GM041371-11 (1999): $181661
2R01GM041371-10 (1998): $178769
Sponsored Links Excellgen http://Excellgen.com
PEPTIDE RECOGNITION BY CLASS I MHC PROTEINS
Barry H Honig, Professor
Columbia Univ New York Morningside Research Administration New York, Ny 100277003
Grant 5P41RR006892-100009 from National Center For Research Resources
Abstract: Thisprojectisverysimilartothepreviousoneinthatweare trying to calculate relative binding energies of different peptides to a single protein whose structure is known. Our goal in this project is to elucidate the principles of specific peptide recognition, a problem of far-reaching implications in biology. We are trying now to identify those interactions that give rise to specificity by calculating the contributions of individual amino acids to the binding energy.
Keywords: biological product, biomedical resource, computer, protein, statistics /biometry, technology /technique
Project start date: 2000-05-05
Project end date: 2002-04-30
BINDING OF CHARGED PEPTIDES And PROTEINS TO LIPID BILAYERS
Barry H Honig, Professor
Columbia Univ New York Morningside Research Administration New York, Ny 100277003
Grant 5P41RR006892-100011 from National Center For Research Resources
Abstract: Thephysicalforcesthatdeterminethebindingofproteinstothe surface of membranes is a problem of central biological importance through its relationship to signal transduction pathways. We are using continuum electrostatics to study this problem in collaboration with the group of Stuart McLaughlin who is measuring binding affinities as a function of lipid composition and salt. This work has been carried out using a parallel version of DelPhi written by Nir Ben-Tal and implemented on the CM-5.
Keywords: biological product, biomedical resource, computer, protein, statistics /biometry, technology /technique
Project start date: 2000-05-05
Project end date: 2002-04-30
ELECTROSTATIC INTERACTIONS IN DNA
Barry H Honig, Professor
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 5R01GM041371-07 from National Institute Of General Medical Sciences IRG: BBCB
Abstract: The primary goal of the proposed research is a detailed understanding of the relationships between structure and free energy that govern conformational changes and binding reactions of nucleic acids. The research involves the continued development of theoretical approaches and their application to problems of biological interest. The basic approach is to describe solute molecules in atomic detail while employing a macroscopic of the solvent. Electrostatic potentials are obtained from finite difference solutions to the Poisson-Boltzmann equation (the FDPB method). The potentials are then used to calculate electrostatic free energies, using an expression derived in the previous funding period. Non-polar contributions are calculated from free energy/surface area relationships. The applications will focus on three classes of problems. 1) Salt effects on the binding of ligands to DNA. Electrostatic potentials around different forms of DNA and RNA will be calculated and compared to results obtained from spin label experiments. The salt dependence of the association constant of drugs that bind in the minor groove, as well as of a number of proteins, will be calculated and compared to experiment. The pH dependence of protein-DNA recognition will also be considered. Model calculations will be used to define possible mechanisms of sequence- specific recognition. The relationship of the total free energy obtained from the PB equation to the predictions of the widely used counterion condensation theory will be explored. 2) Salt independent contributions to binding will be calculated. Experimental comparisons will be made to the measured relative binding free energies of different drugs, and to the results of mutation experiments which modify the binding of different proteins to DNA. In this context an attempt will be made to understand free energy changes associated with hydrophobic and hydrogen bonding mutations. 3) General methods to include solvent and salt effects in the conformational analysis of nucleic acids will be developed. Solvation free energies will be added to the gas phase energies obtained from standard force fields. The effects of solvent and base sequence on the relative free energies of A, B and Z DNA will be calculated. The effects of base sequence on the stability of DNA and RNA loops will also be considered. The health relatedness of these problems results primarily from the fundamental biological importance of understanding nucleic acid structure and function. In addition, drugs that bind to DNA have many therapeutic applications.
Keywords: DNA, conformation, electrical potential, ionic bond, nucleic acid structure, thermodynamics, DNA binding protein, RNA, acidity /alkalinity, chemical binding, computer program /software, computer simulation, divalent cation, electrolyte, hydropathy, ionic strength, ligand, magnesium, mathematical model, nucleic acid inhibitor, nucleic acid sequence, salt, solvent, water solution, electron spin resonance spectroscopy
Project start date: 1988-12-01
Project end date: 1997-11-30
5R01GM041371-07 (1995): $170342
2R01GM041371-06 (1994): $185613
5R01GM041371-09 (1997): $209996
COMPUTER STUDIES OF PROTEIN STRUCTURE AND FUNCTION
Barry H Honig, Professor
Biochem & Molecular Biophysicscolumbia University Health Sciences
columbia University Medical Center
new York, Ny 100323702
Grant 5R37GM030518-18 from National Institute Of General Medical Sciences IRG: BBCA
Abstract: The primary goal of the proposed research is a detailed understanding of the relationships between structure and energy that determine the structure and functions of proteins. A major focus will be the development and application methods for the study of problems such as protein folding and protein stability and the prediction of binding free energies of substrates to proteins. In most applications, relative free energies in solution will be obtained by combining gas phase molecular mechanics calculation with the evaluation of solvation free energies. Electrostatic contributions to solvation are obtained from numerical solutions to the Poisson-Boltzmann (PB) equation. Non-polar contributions are calculated from free energy/surface area relationships. The methodological emphasis will involve the development of algorithms which yield rapid and accurate numerical solutions to the PB equation. The goal is to reach the point where a solvation free energy calculation on a molecule is as fast as a gas phase energy evaluation in molecular mechanics program. This will make it possible to include solvent directly in conformational search procedures, energy minimization and molecular dynamics. Preliminary estimates suggest that a combination of multigriding and adaptive gridding techniques make this a reasonable goal. Methods involving surface charges will also be developed to calculate forces on atoms directly from PB calculations. Proposed research on protein folding will focus on three areas. l) A recently developed method to calculate the pH dependence of protein stability will be used to study acid denaturation. The stability of the compact "molten globule" states formed under acidic conditions will be considered in this context. 2) The factors that determine secondary structure stability, including individual amino acid propensities, will be elucidated with calculations of relative conformational energies. 3) A method to distinguish stable from unstable protein conformations will be developed. Calculations will be carried out of the relative binding energies of different inhibitors to the HIV protease. Studies will be made of compounds for which both structural and thermodynamic data are available. Similar studies will also be carried out on the binding of peptides to class I MHC proteins. High resolution structures are currently available for the binding of different peptides to the same class I protein and binding affinities have also been measured. An attempt will be made to understand the energetic principles and structural rules involved in antigen recognition. The health relatedness of the proposed research is in the general principles about protein structure and function that are being developed. In addition the results of the research will be applicable to structure- based drug design in general, with specific applications to the design of HIV protease inhibitors and to the design of antiviral drugs that act on MHC proteins
Keywords: computer program /software, computer simulation, conformation, method development, protein structure /function, thermodynamics MHC class I antigen, acidity /alkalinity, aspartic endopeptidase, biophysics, chemical binding, chemical stability, computer system design /evaluation, cytochrome c, dielectric property, intermolecular interaction, ionic bond, ionic strength, ionization constant, mathematical model, pancreatic ribonuclease, protease inhibitor, protein denaturation, protein folding, water solution
Project start date: 1981-09-01
Project end date: 1999-11-30
5R37GM030518-18 (1999): $299633
Sponsored Links Excellgen http://Excellgen.com
5R37GM030518-16 (1997): $270445
5R37GM030518-17 (1998): $289963
BINDING OF CHARGED PEPTIDES & PROTEINS TO LIPID BILAYERS
Barry H Honig, Professor
Institution:
Grant 2P41RR006892-060010 from National Center For Research Resources
Abstract: The physical forces that determine the binding of proteins to the surface of membranes is a problem of central biological importance through its relationship to signal transduction pathways. We are using continuum electrostatics to study this problem in collaboration with the group of Stuart McLaughlin who is measuring binding affinities as a function of lipid composition and salt. This work has been carried out using a parallel version of DelPhi written by Nir Ben-Tal and implemented on the CM-5.
Computer Studies Of Protein Structure And Function
Barry H Honig, Professor
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 5R01GM030518-26 from National Institute Of General Medical Sciences IRG: ZRG1
Abstract: The long-range goals of the proposed research are; a) developing computational tools for the calculation of the physical properties of proteins based on three dimensional structure, b) protein-structure prediction, c) understanding the structural and energetic origins of specificity in protein-protein interactions. The specific goals of the current proposal include the development of new methods for homology modeling and studies on specificity determinants in the cadherins, a family of cell-cell adhesion proteins. The health relatedness of the proposed research involves the development of tools for a variety of biological applications and the discovery of new insights about fundamental biological processes such as those involved in tissue formation. The proposed research on homology modeling includes 1) the development, testing and application of methods to evaluate the conformational energies of proteins and to refine three dimensional structures; 2) the development, testing and application of methods for structure-based sequence alignment; 3) the development of a new approach for generating "suboptimal" alignments and evaluating models that are generated from these alignments based on conformational energies and other scoring functions. The work on cadherins involves applications of many of the methods being developed. Cadherins are a family of proteins present on the surfaces of the cells that mediate selective intercellular adhesion. The goal of the proposed research is to understand how cadherin domains, many of which have high degrees of sequence and structural similarity, can bind to one another in a specific manner. The work involves a collaborative experimental component. The computational work involves studying specificity determinants in cadherin domains whose structure are known, the construction of homology models for other family members, and the use of the various structures to identify key residues that play a role in specificity.
Keywords: cadherin, computational biology, computer program /software, computer simulation, conformation, protein structure function, structural biology, chemical binding, chemical model, chemical stability, computer system design /evaluation, intermolecular interaction, model design /development, protein folding, thermodynamics, computer data analysis
Project start date: 1981-09-01
Project end date: 2008-11-30
5R01GM030518-26 (2007): $249130
5R01GM030518-25 (2006): $254931
2R01GM030518-24 (2005): $259458
5R01GM030518-13 (1994): $227124
5R01GM030518-12 (1993): $219678
5R01GM030518-11 (1992): $220210
ELECTROSTATIC INTERACTIONS IN DNA
Barry H Honig, Professor
Columbia Univ New York Morningside Research Administration New York, Ny 100277003
Grant 5R01GM041371-05 from National Institute Of General Medical Sciences IRG: BBCA
Abstract: The long term objectives of the research described in this proposal are to understand the structure and function of biological macromolecules at the molecular level. The proposal describes a theoretical approach to the understanding of the conformation and dynamics of DNA. The focus is on electrostatic interactions and, in particular, on the contribution of solvation and ionic strength effects in screening pairwise electrostatic interactions and in stabilizing and destabilizing different DNA conformations as well as ligand-DNA interactions. The specific aims include i) The development of methods to obtain total electrostatic energies from a complete Poisson-Boltzmann treatment of DNA conformation and ligand-DNA interactions. ii) The incorporation of the methods and results of a Poisson-Boltzmann treatment of solvent into molecular mechanics calculations and the application of these simulations to different phenomena. iii) The calculation of electrostatic potentials and ion distributions around different forms of DNA. iv) Calculating electrostatic contributions to conformational changes in DNA. v) Calculating electrostatic contributions to ligand-DNA binding energies. vi) Carrying out Monte-Carlo simulations of the ion atmosphere and of water structure around DNA. The basic approach is to use a model which combines a detailed atomic-level of the DNA with a continuum treatment of the solvent. Electrical potentials are obtained by solving the non-linear Poisson Boltzmann equation, accounting for the charge distribution of the DNA, for the different polarizabilities of the macromolecule and solvent and for the effects of the ion atmosphere. The Poisson-Boltzmann equation is solved numerically using a finite difference approach applied previously to proteins. The health relatedness of the research is in the potential it offers in understanding DNA structure and function, and more specifically, in the insights and methodology it will provide for rational drug design.
Keywords: DNA, conformation, electrical potential, computer simulation, dielectric property, ion, ionic strength, ligand, mathematical model, solution, thermodynamics
Project start date: 1988-12-01
Project end date: 1993-11-30
5R01GM041371-05 (1993): $118522
Sponsored Links Excellgen http://Excellgen.com
5R01GM041371-04 (1992): $118809
Computer Studies Of Protein Structure And Function
Barry H Honig, Professor
Joint Centers For Systems Biologycolumbia University Health Sciences
Grant 2R01GM030518-28 from National Institute Of General Medical Sciences IRG: MSFB
Abstract: The goals of the proposed research include a) The development of methods and associated computational tools that use three-dimensional structural information to predict protein function. b) The development of methods for the integration of structural information in the generation of networks of protein- protein interactions (interactomes). c) The application of structural information in the creation of an interactome of human and tumor B-cells and the use of this network in applications to B-cell Biology. These research goals are motivated by a number of factors. First, there is a general sense that structural information, as provided for example by the Protein Structure Initiative (PSI) is not fully exploited by the wider biological community. An interactive function prediction server is being developed with this issue in mind. Second, Structural Biology has not been fully integrated into Systems Biology approaches to predict protein networks and it would be extremely valuable to try to increase the integration of the two fields. Third, human B-cell phenomena are of great biological and medical interest and there is an exciting opportunity to incorporate structural information into this field in a novel way. A central element of the approach to be taken is the use of structural alignments to reveal novel functional relationships between proteins that have been classified as belonging to different protein "folds". Evidence is provided that there is a wealth of functional information in such remote relationships and computational tools to mine and visualize this information will be developed. The research design also includes the of a novel approach to use structural alignments to identify potential protein-protein ligand, protein-protein and protein-DNA binding partners and to identify interfacial residues in the complexes they form. A novel scoring scheme for protein-protein interactions will be developed and a database of potential complexes, designed originally for human proteins, will be constructed. The database will also identify complexes that are unlikely to form. The information in this database will be incorporated into a Baysian inference scheme and used in the construction of a "structure-enabled" B-cell Interactome. The relevance of the proposed research to public health lies in part in the insights, and accompanying methods, that will be provided about structure/function relationships in proteins. Specific applications to B-cell Biology have direct relevance to understanding a variety of B-cell related cancers
Project start date: 1981-09-01
Project end date: 2012-11-30
TRAINING PROGRAM IN COMPUTATIONAL BIOLOGY
Barry H Honig, Principal Investigator
Columbia University Health Sciences, Columbia University Medical Center, New York, Ny 10032-3702
Grant 5T32GM082797-03 from National Institute Of General Medical Sciences
Abstract: The aim of the training program that we are proposing is to educate a generation of scientists who have the knowledge required to identify important biological problems and the expertise required to develop and apply advanced computational methods towards their solution. The scientist we envision will be an integral part of a discipline involving computational science but will be comfortable attending a meeting of experimental biologists as well. Indeed we believe that it is essential that the next generation of computational biologists have a deep understanding of biology. In addition it is important that they have familiarity with more than one computational discipline. For example, it would be desirable if computer scientists working on new algorithms to classify proteins would understand structural biology and have expertise in computational studies of protein structure and function as well. Integrating different computational disciplines is a challenging goal in its own right and is made more complex by the fact that the unifying theme is biological. We will ensure that our trainees have a deep understanding of experimental biology, have expertise in at least one area of computational biology and have familiarity with other areas
Keywords: Computational Biology; Training Programs
Project start date: 2008-07-01
Project end date: 2013-06-30
Budget start date: 1-JUL-2010
Budget end date: 30-JUN-2011
PFA/PA: PA-06-468
5T32GM082797-03 (2010): $131203
5T32GM082797-02 (2009): $130542
1T32GM082797-01 (2008): $86588
3T32GM082797-02S1 (2009): $87028
CONFORMATION OF SMALL PEPTIDES IN SOLUTION
Barry H Honig, Professor
Columbia Univ New York Morningside Research Administration New York, Ny 100277003
Grant 5P41RR006892-100008 from National Center For Research Resources
Abstract: DysonandWrighthaveused2DNMRtodeterminetheconformations of small penta-peptides in solution. Remarkably, some of these peptides have a single favored conformation. We are in the process of generating an ensemble of possible conformations and calculating their conformational energies to see if we can account for the experimental observations. If we are successful, we will suggest new peptides to be studied in an attempt to see if our methods have predictive power. This project is one part of a larger effort going on in the Center to elucidate the energetic basis of protein folding and to develop prediction algorithms.
Keywords: biological product, biomedical resource, computer, statistics /biometry, technology /technique
Project start date: 2000-05-05
Project end date: 2002-04-30
Sponsored Links Excellgen http://Excellgen.com
COMPUTER STUDIES OF PROTEIN STRUCTURE AND FUNCTION
Barry H Honig, Principal Investigator
Columbia University Health Sciences, Columbia University Medical Center, New York, Ny 10032-3702
Grant 5R01GM030518-29 from National Institute Of General Medical Sciences
Keywords: 3-D structure; 3-dimensional structure; 3D structure; Address; Area; B blood cells; B cell tumor; B-Cell Lymphocytic Neoplasm; B-Cell Neoplasm; B-Cells; B-Lymphocytes; B-lineage tumor; Binding; Binding (Molecular Function); Binding Proteins; Bio-Informatics; Bioinformatics; Biological; Bursa-Dependent Lymphocytes; Bursa-Equivalent Lymphocyte; Cadherins; Cancers; Cellular biology; Communities; Complex; DNA-Binding Proteins; Data Banks; Data Bases; Databank, Electronic; Databanks; Database, Electronic; Databases; Development; Elements; Expression Profiling; Expression Signature; Family; Funding; GeneHomolog; Generations; Goals; Homeo Domain; Homolog; Homologous Gene; Homologue; Homology Modeling; Human; Human, General; Learning, Machine; Ligand Binding Protein; Ligands; Liver Cell Adhesion Molecules; Location; Machine Learning; Malignant Neoplasms; Malignant Tumor; Man (Taxonomy); Man, Modern; Medical; Membrane Proteins; Membrane-Associated Proteins; Methods; Mind; Mining; Minings; Modeling; Molecular Fingerprinting; Molecular Interaction; Molecular Profiling; Ontology; PSI; Programs (PT); Programs [Publication Type]; Progress Reports; Protein Binding; Protein Family; Protein Structure Initiative; Proteins; Public Health; Reports, Progress; Research; Research Design; Role; Scheme; Specificity; Structure; Structure-Activity Relationship; Study Type; Surface Proteins; Systems Biology; Testing; Ubiquitin Like Proteins; Work; base; cell biology; chemical structure function; clinical data repository; clinical data warehouse; computational studies; computational tools; computer studies; computerized tools; data repository; design; designing; develop software; developing computer software; gene product; homeodomain; insight; interest; interfacial; kernel methods; liver cell adhesion molecule; malignancy; method development; molecuar profile; molecular signature; neoplasm/cancer; new approaches; novel; novel approaches; novel strategies; novel strategy; programs; protein complex; protein folding; protein function; protein protein interaction; protein structure; protein structure function; public health medicine (field); public health relevance; relational database; social role; software development; statistical learning; structural biology; structural genomics; structure function relationship; study design; support vector machine; three dimensional structure; tool; tumor
Relevance: The relevance of the proposed research to public health lies in part in the insights, and accompanying methods, that will be provided about structure/function relationships in proteins. Specific applications to B-cell Biology have direct relevance to understanding a variety of B-cell related cancers
Project start date: 1981-09-01
Project end date: 2012-11-30
Budget start date: 1-DEC-2009
Budget end date: 30-NOV-2010
PFA/PA: PA-07-070
5R01GM030518-29 (2010): $265694
5R37GM030518-23 (2004): $299739
Center For Computational Biology And Bioinformatics
Barry H Honig, Professor
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 5P20LM007276-03 from National Library Of Medicine IRG: ZRG1
Project start date: 2001-09-30
Project end date: 2005-08-31
5P20LM007276-03 (2003): $709613
COMPUTER STUDIES OF PROTEIN STRUCTURE AND FUNCTION
Barry H Honig, Professor
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 5R37GM030518-22 from National Institute Of General Medical Sciences IRG: NSS
Keywords: computer program /software, computer simulation, conformation, method development, protein structure function, thermodynamics, MHC class I antigen, acidity /alkalinity, aspartic endopeptidase, biophysics, chemical binding, chemical stability, computer system design /evaluation, cytochrome c, dielectric property, intermolecular interaction, ionic bond, ionic strength, ionization constant, mathematical model, pancreatic ribonuclease, protease inhibitor, protein denaturation, protein folding, water solution
Project start date: 1981-09-01
Project end date: 2004-11-30
5R37GM030518-22 (2003): $291107
5R37GM030518-21 (2002): $282725
5R37GM030518-20 (2001): $274590
4R37GM030518-19 (2000): $387806
TRAINING PROGRAM IN MOLECULAR BIOPHYSICS
Barry H Honig, Professor
Biochem & Molecular Biophysicscolumbia University Health Sciences
columbia University Medical Center
new York, Ny 100323702
Grant 5T32GM008281-13 from National Institute Of General Medical Sciences IRG: ZGM1
Project start date: 1988-09-30
Project end date: 2003-06-30
5T32GM008281-13 (2000): $243564
5T32GM008281-12 (1999): $234171
Sponsored Links Excellgen http://Excellgen.com