SimBioSys Inc.© 2001http://www.simbiosys.ca/ New methods for studying receptor-ligand interactions Zsolt Zsoldos, Aniko Simon SimBioSys Inc.,

Slides:

Advertisements

Similar presentations

Scientific & technical presentation Structure Visualization with MarvinSpace Oct 2006.

Advertisements

1 Miklós Vargyas, Judit Papp May, 2005 MarvinSpace – live demo.

Chapter 21 Electric Charge and Electric Field. Charles Allison © 2000 Question An  particle with a charge +2e and a mass of 4m p is on a collision course.

Your tests and the printouts with all your scores are in the folder with your name on the front desk. Inform me of any errors on the printout. Assignment.

Homework 2 (due We, Feb. 5): Reading: Van Holde, Chapter 1 Van Holde Chapter 3.1 to 3.3 Van Holde Chapter 2 (we’ll go through Chapters 1 and 3 first. 1.Van.

1 Physical Chemistry III Molecular Interactions Piti Treesukol Chemistry Department Faculty of Liberal Arts and Science Kasetsart University :

1 ELECTROSTATICS COULUMB’S LAW ELECTRIC FIELD INTENSITY LINE, SURFACE & VOLUME CHARGES ELECTRIC FLUX DENSITY GAUSS’S LAW ELECTRIC POTENTIAL BOUNDARY CONDITIONS.

Lecture 14: Special interactions. What did we cover in the last lecture? Restricted motion of molecules near a surface results in a repulsive force which.

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

Chemistry 6440 / 7440 Molecular Mechanics. Resources Grant and Richards, Chapter 3 Leach, Chapter 3 Jensen, Chapter 2 Cramer, Chapter 2 Burkert and Allinger,

Crystal Binding (Bonding) Continued

Computational Experiments with a Lone-Pair Based Hydrogen-Bonding Energy Function in Mini-Rosetta YOUR NAME HERE (Arial 28 pt italic)YOUR PROJECT URL HERE.

FORCES GOVERNING BIOLOGICAL SYSTEMS. Electronic structure of atoms Negatively charged electrons revolve around positively charged nucleus. Atom.

SimBioSys Inc.© 2003http:// eHiTS: Novel algorithm for fast, exhaustive flexible ligand docking and scoring Zsolt Zsoldos, Aniko Simon,

Intermolecular Forces. Intermolecular forces are weak, short-range attractive forces between atoms or molecules. Intermolecular forces ultimately derive.

Intermolecular Forces. Intermolecular forces are weak, short-range attractive forces between atoms or molecules. Intermolecular forces ultimately derive.

Molecular Dynamics, Monte Carlo and Docking Lecture 21 Introduction to Bioinformatics MNW2.

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

Molecular Modeling of Crystal Structures molecules surfaces crystals.

27 August, 2004 Chapters 2-3 Nucleic Acid Structure and Weak Bonds.

Quantitative Structure-Activity Relationships (QSAR) Comparative Molecular Field Analysis (CoMFA) Gijs Schaftenaar.

College 3. Huckel voor 1,3 butadiene CH2=CHCH=CH2 C atomen: 3 sp 2 hybidide orbitalen h1, h2, h3 2 e - in 1s 3 e - in h1, h2, h3 1 e- over voor π orbitaal.

Bioinformatics IV Quantitative Structure-Activity Relationships (QSAR) and Comparative Molecular Field Analysis (CoMFA) Martin Ott.

Development and Validation of a Genetic Algorithm for Flexible Docking Gareth Jones, Peter Willet, Robert C. Glen, Andrew R. Leach and Robin Taylor J.

Polarity of Bonds Molecular Polarity. Equal Pull on Electrons If there is no difference in the electronegativity of the atoms forming a covalent bond,

1 Physical Chemistry III Molecular Interactions Piti Treesukol Chemistry Department Faculty of Liberal Arts and Science Kasetsart University :

BINF6201/8201 Principle components analysis (PCA) -- Visualization of amino acids using their physico-chemical properties

How H 2 0 interacts with: Itself –Hydrogen-bonding Ions and charged functional groups –Solvation, screening, dielectric value Non-polar groups –The hydrophobic.

Molecular Modeling Part I. A Brief Introduction to Molecular Mechanics.

AS Chemistry – Atomic structure and bonding. Sub-atomic particles Protons – mass 1; charge +1 Electrons – mass 1 / 1840 ; charge –1 Neutrons – mass 1;

Chapter 12 Intermolecular Forces: Liquids, Solids, and Phase Changes.

02/03/10 CSCE 769 Dihedral Angles Homayoun Valafar Department of Computer Science and Engineering, USC.

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

Chicago, July 22-23, 2002DARPA Simbiosys Review 1 Monte Carlo Particle Simulation of Ionic Channels Trudy van der Straaten Umberto Ravaioli Beckman Institute.

18.5 Coulomb's Law. The magnitude F of the electrostatic force exerted by one point charge on another point charge is directly proportional to the magnitudes.

 Receptors are mostly membrane-bound proteins that selectively bind small molecules called ligands which results in physiological response.  They are.

Automotive Soiling Simulation Based On Massive Particle Tracing Stefan Röttger Martin Schulz Wolf Bartelheimer Thomas Ertl Visualization and Interactive.

Coulomb’s Law Performing electric field calculations on charge distributions in an X-Y coordinate Plane.

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

SimBioSys Inc.© 2004http:// Conformational sampling in protein-ligand complex environment Zsolt Zsoldos SimBioSys Inc., © 2004 Contents:

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Chapter 2: The chemical basis of life.

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

Covalent interactions non-covalent interactions + = structural stability of (bio)polymers in the operative molecular environment 1 Energy, entropy and.

Virtual Screening C371 Fall INTRODUCTION Virtual screening – Computational or in silico analog of biological screening –Score, rank, and/or filter.

Homework 2 (due We, Feb. 1): Reading: Van Holde, Chapter 1 Van Holde Chapter 3.1 to 3.3 Van Holde Chapter 2 (we’ll go through Chapters 1 and 3 first. 1.Van.

Lecture 5 Barometric formula and the Boltzmann equation (continued) Notions on Entropy and Free Energy Intermolecular interactions: Electrostatics.

Coulomb’s Law Physics 12. Electroscope ► Draw a diagram showing the forces that exist on the leaves of the electroscope when it is placed close to the.

Thermodynamics of Associating Fluids 1. Chains of molecules Many molecules are not spherical, but could be represented as consisting of connected spherical.

Lab 1: Electric Fields and Gauss’s Law Only 11 more labs to go!! When we study electrostatics we talk about stationary charges. Electric charges will be.

Molecular Mechanics (Molecular Force Fields). Each atom moves by Newton’s 2 nd Law: F = ma E = … x Y Principles of M olecular Dynamics (MD): F =

Chapter 16 Electric Charge and Electric Field. Units of Chapter 16 Static Electricity; Electric Charge and Its Conservation Electric Charge in the Atom.

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

Introduction-2 Important molecular interactions in Biomolecules

Intermolecular Interactions

Hydrogen bonding.

Intermolecular binding forces

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

Chapter 2 Molecular Mechanics

Intermolecular Forces

Intermolecular Forces

CZ3253: Computer Aided Drug design Lecture 4: Structural modeling of chemical molecules Prof. Chen Yu Zong Tel:

Intermolecular attractions

Volume 3, Issue 3, Pages (March 1999)

Patrick: An Introduction to Medicinal Chemistry 6e

Analysis of crystal structures

Physical Chemistry Chapter VI Interaction between Molecules 2019/5/16

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:

SimBioSys Inc.© 2001http:// New methods for studying receptor-ligand interactions Zsolt Zsoldos, Aniko Simon SimBioSys Inc., Efficient grid-based force field calculations on protein structures to evaluate, visualise and help to improve the binding of lead structures.

SimBioSys Inc.© 2001http:// Contents of the presentation Next generation grid technology Configurable interaction force fields Force field visualisation techniques Results on Trypsin - APPA Ras P21 - GDP COX2 - SC558

SimBioSys Inc.© 2001http:// Grid resolution problem 1.6Å 7K points 0.3 MB 0.22 min 50% error 1.0Å 30K points 1.3 MB 1 min 20%error 0.5Å 250K points 11 MB 8 min 8% error 0.16Å 7300K points 321 MB 216 min 2% error

SimBioSys Inc.© 2001http:// Variable resolution grids Grid spacing 0.15 Å -3.0 Å Memory and CPU (build) ~1 Å -1.5 Å grid equivalent Precision for ligand atoms ~0.15 Å grid equivalent Octree, hashing Hierarchical grid: constant access time 0.15Å-3.0Å variable 28K points 1.5 MB 1 min 2%

SimBioSys Inc.© 2001http:// Interaction Force Fields 1. Van der Waals: Lennard Jones Electrostatics: Coulomb Parameters based on AMBER Partial charges of H-bond acceptors are distributed to the lone pairs at 1 Å distance from the heavy atom Lp O C - -

SimBioSys Inc.© 2001http:// Interaction Force Fields 2. Hydrogen bond term: A-H and D-Lp distances Proton directionality: cos 2  D-H-A) Lone pair directionality: cos(A-Lp-H) Optimum directionality vectors Multiple receptor atom effects Separate donor, acceptor grids D H A Lp

SimBioSys Inc.© 2001http:// Interaction Force Fields 3. Hydrophobicity term: Distance dependent functions (e.g. Lennard-Jones) Polar repulsion component Clash penalty component Activity flags (assigned using knowledge base) Highly configurable setup Smooth functions

SimBioSys Inc.© 2001http:// Force field visualization techniques 2D surfaces Molecular surface map Contour iso-surface Color coded cut plane True 3D visualisation Volume rendering

SimBioSys Inc.© 2001http:// APPA electro and H-bond fields with Volume Rendering

SimBioSys Inc.© 2001http:// APPA H-bond donor field visualisations

SimBioSys Inc.© 2001http:// Trypsin forces compared to APPA atoms

SimBioSys Inc.© 2001http:// Ras P21H-bond acceptor field with GDP

SimBioSys Inc.© 2001http:// Ras P21 H-bond donor field with GDP

SimBioSys Inc.© 2001http:// Ras P21 electrostatic and H-bond fields compared to GDP ligand atoms

SimBioSys Inc.© 2001http:// COX- 2 hydrophobicity field with SC558

SimBioSys Inc.© 2001http:// COX-2 electrostatics with SC558

SimBioSys Inc.© 2001http:// Conclusion "No compromise" solution to eliminate the well known grid resolution problem Force Field validation - looking for collaborators Volume rendering is "The Ultimate" solution for 3D force field visualisation - now available with interactive speed on cheap PC hardware The “InterView” software

SimBioSys Inc.© 2001http:// Acknowledgements Timur Skeini, Irina and Zsolt Szabo Peter Johnson & ICAMS - consultations Linux community - development platform nVidia, ATI etc. - fast volume rendering The organizers - opportunity The audience - attention and patience