Rong Chen Boston University

Slides:

Advertisements

Similar presentations

Scientific & technical presentation Structure Visualization with MarvinSpace Oct 2006.

Advertisements

Ugur Sezerman Sabanci University

Protein Docking Rong Chen Boston University. BU Bioinformatics The Lowest Binding Free Energy  G water R L R L L R L R L R.

Rosetta Energy Function Glenn Butterfoss. Rosetta Energy Function Major Classes: 1. Low resolution: Reduced atom representation Simple energy function.

How to approximate complex physical and thermodynamic interactions? Employ rigid or flexible structures for ligand and receptor (Side-chains or Back-bone.

Iterative Relaxation of Constraints (IRC) Can’t solve originalCan solve relaxed PRMs sample randomly but… start goal C-obst difficult to sample points.

BDOCK ： An Implementation of the FFT Protein-Protein Docking Method Using the BALL Library Bingding Huang Center of Bioinformatics Saarland University.

Molecular Docking G. Schaftenaar Docking Challenge Identification of the ligand’s correct binding geometry in the binding site ( Binding Mode ) Observation:

8. Protein Docking 1. Prediction of protein-protein interactions 1.How do proteins interact? 2.Can we predict and manipulate those interactions?  Prediction.

Two Examples of Docking Algorithms With thanks to Maria Teresa Gil Lucientes.

Protein Docking and Interactions Modeling CS 374 Maria Teresa Gil Lucientes November 4, 2004.

Protein Primer. Outline n Protein representations n Structure of Proteins Structure of Proteins –Primary: amino acid sequence –Secondary:  -helices &

FLEX* - REVIEW.

An Integrated Approach to Protein-Protein Docking

BL5203: Molecular Recognition & Interaction Lecture 5: Drug Design Methods Ligand-Protein Docking (Part I) Prof. Chen Yu Zong Tel:

Packing, Cavities atomic radii, contact- distance profiles cavities P-P interactions crystal contacts solvent channels de-stabilizing mutations in core.

Structure-Function Analysis 117 Jan 2006 DNA/Protein structure-function analysis and prediction Protein-protein Interaction (PPI) and Docking: Protein-protein.

CAPRI Critical Assessment of Prediction of Interactions.

Protein Structure Prediction Samantha Chui Oct. 26, 2004.

Protein-protein and Protein- ligand Docking The geometric filtering.

The Geometry of Biomolecular Solvation 1. Hydrophobicity Patrice Koehl Computer Science and Genome Center

Inverse Kinematics for Molecular World Sadia Malik April 18, 2002 CS 395T U.T. Austin.

Bioinf. Data Analysis & Tools Molecular Simulations & Sampling Techniques117 Jan 2006 Bioinformatics Data Analysis & Tools Molecular simulations & sampling.

Comparative Evaluation of 11 Scoring Functions for Molekular Docking Authors: Renxiao Wang, Yipin Lu and Shaomeng Wang Presented by Florian Lenz.

Computational Structure Prediction Kevin Drew BCH364C/391L Systems Biology/Bioinformatics 2/12/15.

QSAR Qualitative Structure-Activity Relationships Can one predict activity (or properties in QSPR) simply on the basis of knowledge of the structure of.

Molecular Docking S. Shahriar Arab. Overview of the lecture Introduction to molecular docking: Definition Types Some techniques Programs “Protein-Protein.

BIOC3010: Bioinformatics - Revision lecture Dr. Andrew C.R. Martin

Molecular Mechanics and docking Lecture 22 Introduction to Bioinformatics 2007 C E N T R F O R I N T E G R A T I V E B I O I N F O R M A T I C S V U E.

Jeremy C. Smith, University of Heidelberg Introduction to Protein Simulations and Drug Design R P.

ClusPro: an automated docking and discrimination method for the prediction of protein complexes Stephen R. Comeau, David W.Gatchell, Sandor Vajda, and.

Structure-Function Analysis 117 Jan 2006 DNA/Protein structure-function analysis and prediction Protein-protein Interaction (PPI): Protein-protein Interaction.

Marcin Pacholczyk, Silesian University of Technology.

 Four levels of protein structure  Linear  Sub-Structure  3D Structure  Complex Structure.

Flexible Multi-scale Fitting of Atomic Structures into Low- resolution Electron Density Maps with Elastic Network Normal Mode Analysis Tama, Miyashita,

In silico discovery of inhibitors using structure-based approaches Jasmita Gill Structural and Computational Biology Group, ICGEB, New Delhi Nov 2005.

25. Lecture WS 2008/09Bioinformatics III1 V25 – protein docking, FFT Fast Fourier Transform.

Conformational Entropy Entropy is an essential component in ΔG and must be considered in order to model many chemical processes, including protein folding,

SimBioSys Inc.© Slide #1 Enrichment and cross-validation studies of the eHiTS high throughput screening software package.

Altman et al. JACS 2008, Presented By Swati Jain.

1/20 Study of Highly Accurate and Fast Protein-Ligand Docking Method Based on Molecular Dynamics Reporter: Yu Lun Kuo

Discrimination of near-native structures by clustering docked conformations and the selection of the optimal radius D. Kozakov 1, K. H. Clodfelter 2, C.

Protein Folding & Biospectroscopy Lecture 6 F14PFB David Robinson.

Structure- based Structure-based computer-aided drug discovery (SB-CADD) approach: helps to design and evaluate the quality, in terms of affinity, of series.

Coarse and Reliable Geometric Alignment for Protein Docking Yusu Wang Stanford University Joint Work with P. K. Agarwal, P. Brown, H. Edelsbrunner, J.

Surflex: Fully Automatic Flexible Molecular Docking Using a Molecular Similarity-Based Search Engine Ajay N. Jain UCSF Cancer Research Institute and Comprehensive.

Mean Field Theory and Mutually Orthogonal Latin Squares in Peptide Structure Prediction N. Gautham Department of Crystallography and Biophysics University.

Local Flexibility Aids Protein Multiple Structure Alignment Matt Menke Bonnie Berger Lenore Cowen.

Elon Yariv Graduate student in Prof. Nir Ben-Tal’s lab Department of Biochemistry and Molecular Biology, Tel Aviv University.

Protein-Protein Interactions. A Protein may interact with: –Other proteins –Nucleic Acids –Small molecules Protein Interactions.

1 of 21 SDA development -Description of sda Description of sda-5a - Sda for docking.

Structural Bioinformatics Elodie Laine Master BIM-BMC Semester 3, Genomics of Microorganisms, UMR 7238, CNRS-UPMC e-documents:

Research Overview III Jack Snoeyink UNC Chapel Hill.

CHM 708: MEDICINAL CHEMISTRY

Computational Structure Prediction

Simplified picture of the principles used for multiple copy simultaneous search (MCSS) and for computational combinatorial ligand design (CCLD). Simplified.

Computational design of protein function

International Chemical Design & Discovery Course 2017

Ligand Docking to MHC Class I Molecules

Do enzyme-inhibiting drugs show increased reliance

An Integrated Approach to Protein-Protein Docking

9. Protein Docking.

Analysis of crystal structures

Complementarity of Structure Ensembles in Protein-Protein Binding

Ligand Binding to the Voltage-Gated Kv1

Protein-Protein Docking: From Interaction to Interactome

Mr.Halavath Ramesh 16-MCH-001 Dept. of Chemistry Loyola College University of Madras-Chennai.

Mr.Halavath Ramesh 16-MCH-001 Dept. of Chemistry Loyola College University of Madras-Chennai.

Mr.Halavath Ramesh 16-MCH-001 Dept. of Chemistry Loyola College University of Madras-Chennai.

Mr.Halavath Ramesh 16-MCH-001 Dept. of Chemistry Loyola College University of Madras-Chennai.

Presentation transcript:

Rong Chen Boston University Protein Docking Rong Chen Boston University

The Lowest Binding Free Energy DG water L R L R R L R L L R

Protein Docking Using FFT Fast Fourier Transform Complex Conjugate Discretize Correlation function Fast Fourier Transform L L Rotate L Discretize Surface Interior

Rotational Sampling Sampling Interval Number of angles 20° 1,800 15° Evenly distributed Euler angles Sampling Interval Number of angles 20° 1,800 15° 3,600 12° 9,000 10° 14,400 8° 27,000 6° 54,000 4° 180,000

Performance Evaluation Success Rate: given the number of predictions(Np), success rate is the percentage of complexes in the benchmark for which at least one hit has been obtained. Hit Count: the average number of hits over all complexes at a particular Np.

Rotational Sampling Density

Rotational Sampling Density

Protein Docking Using FFT Fast Fourier Transform Complex Conjugate Discretize Correlation function Fast Fourier Transform L L Rotate L Discretize Surface Interior

Protein Docking Using FFT Increase the speed by 107 Y Translation Correlation X Translation L R IFFT Surface Interior Binding Site

An Effective Binding Free Energy Function van der Waals energy; Shape complementarity Desolvation energy; Hydrophobicity Electrostatic interaction energy Translational, rotational and vibrational free energy changes Number of atom pairs of type i Desolvation energy for an atom pair of type i

Grid-based Shape Complementarity 1 RGSC LGSC

Pairwise Shape Complementarity 2 3 5 1 RPSC LPSC

PSC vs. GSC on Success Rate

PSC vs. GSC on Hit Count

Why PSC works better than GSC?

Why PSC works better than GSC? D

A Receptor-Ligand Complex

An Effective Binding Free Energy Function van der Waals energy; Shape complementarity Desolvation energy; Hydrophobicity Electrostatic interaction energy Translational, rotational and vibrational free energy changes Number of atom pairs of type i-j Desolvation energy for an atom pair of type i-j

Impact of Desolvation and Electrostatics

Impact of Desolvation and Electrostatics

Other available Docking Software Fast Fourier Transform or FFT (Katchalski-Katzir, Sternberg, Vakser, Ten Eyck groups) Computer vision based method (Nussinov group, 1999) Boolean operations (Palma et al., 2000) Polar Fourier correlations (Ritchie & Kemp, 2000) Genetic algorithm (Gardiner, Burnett groups) Flexible docking (Abagyan, 2002)

3D-Dock Michael J.E. Sternberg, Imperial Cancer Research Fund, London, UK. FTDock: Grid-based shape complementarity, FFT. RPScore: empirical pair potential. MultiDock: refinement. http://www.bmm.icnet.uk/docking/index.html

GRAMM Ilya A. Vakser, State University of New York at Stony Brook. Geometric fit and hydrophobicity FFT Low resolution docking http://reco3.ams.sunysb.edu/gramm/

DOT Lynn F. Ten Eyck, University of California, San Diego. Grid-based shape complemetarity, elctrostatics FFT http://www.sdsc.edu/CCMS/Papers/DOT_sc95.html

ICM Ruben Abagyan, The Scripps Research Institute, La Jolla. Pseudo-Brownian rigid-body docking Biased Probability Monte Carlo Minimization of the ligand interacting side-chains. http://abagyan.scripps.edu/lab/web/man/frames.htm

HEX Dave Ritchie, University of Aberdeen, Aberdeen, Scotland, UK spherical polar Fourier correlations http://www.biochem.abdn.ac.uk/hex/

Approach Overview PDB1 PDB2 PDB Processing Biological information ZDOCK: Initial-stage Docking Biological information RDOCK: Refinement-stage Docking Clustering Final 10 predictions

Example: CAPRI Target 6: α-amylase / Camelid VHH domain