Principles of Drug Design

Size: px
Start display at page:

Download "Principles of Drug Design"

Transcription

1 (16:663:502) Instructors: Longqin Hu and John Kerrigan Direct questions and enquiries to the Course Coordinator: Longqin Hu For more current information, please check WebCT at Tentative Course Outline I. Introduction to The Drug Discovery/Development (Hu) 2 lecture BMC Chp 2 p1-36 and Chp 9 p A. Drug Discovery 1. Definition of Drug Discovery 2. Stages of drug discovery 3. Strategic Issues in drug discovery B.. Drug Development 1. Chemistry 2. Preclinical Studies 3. Transition from Preclinical to Clinical 4. Planning the Drug Development Process 5. Clinical Research C.. Source of Drugs 1. Drugs from Natural Sources (Natural Products) a. Plants b. Animals c. Microorganisms (Fungi, Bacteria) 2. Drugs from Organic Synthesis D. Structural effects on drug action 1. Sequence of events after drug administration 2. Physico-chemical properties that are related to drug action 3. Structurally Non-Specific Drugs 4. Structurally Specific Drugs 5. Role and types of chemical bonding involved in drug-target interactions 6. Steric factors and pharmacological activity E.. The Gleavec Story: discovery and development (Dr. Ray Baktiar, Merck Research Lab)

2 Course Outline Page 2 II. Approaches to New Drug Discovery (Hu) 2 lectures BMC Chp 19 p MCPP Chp p A. Drugs Derived from Natural Products B. Existing Drugs as a Source for New Drug Discovery C. Using Disease Models as Screens for New Drug Leads D. Physiological Mechanisms: the Modern Rational Approach to Drug Design E: Approaches to Lead Optimization 1. Bioisosteric replacement 2. Conformation restriction a. Increase selectivity b. Increase affinity 3. Pharmacophore 4. Molecular dissection 5. Metabolic stabilization III. Enzymes as Targets of Drug Design (Hu) 7 lectures BMC Chp 18 p A. Enzyme kinetics (Hu) 1. The Michaelis-Mention Equation 2. Steady state of an enzyme-catalyzed reaction 3. Validity of the Steady-state assumption 4. Graphs of the Michaelis-Mention Equation 5. Practical aspects of kinetic studies B. Enzyme inhibition and activation (Hu) 1. Reversible and irreversible inhibition 2. Linear inhibition 3. Plotting inhibition results 4. Inhibition by a competing substrate 5. Enzyme activation C. Approaches to the Rational Design of Enzyme Inhibitors (Hu) 1. Transition state analogues 2. Mechanism-based inhibitors 3. Affinity labels D. Farnesyl transferase inhibitors: Design and Synthesis (Dr. Theresa Williams, Merck Research Laboratory, West Point) E. Structure-based design of thrombin inhibitors (Dr. David Kimball, Lexicon Pharmaceuticals) 1. Coagulation cascade 2. Structure of enzyme 3. Structure of enzyme inhibitor complexes 4. Medicinal chemistry 5. The challenges of pharmacokinetics

3 Course Outline Page 3 F. Selective inhibitors of cyclin-dependent kinases (Dr. David Kimball) 1. Kinases 2. Is selective inhibition possible with ATP mimetics? 3. Medicinal chemistry 4. Challenges in vivo IV. Receptors as Targets of Drug Design (Hu) 2 lectures BMC Chp 11 p A. Receptor Theory B. Receptor Complexes and Allosteric Modulators C. Second and Third Messenger Systems D. Molecular Biology of Receptors F. Receptor Models and Nomenclature G. Receptor Binding Assays H. Lead Compound Discovery of Receptor agonists and antagonists 1. Natural Product Sources 2. Pharmacophore-based Ligand Libraries 3. Diversity-based ligand libraries 4. High-throughput screening V. Computer-Aided Drug Design (Kerrigan) 10 lectures A. Molecular Mechanics Force Fields 1. Introduction 2. MM2/MM3/MM4 force fields 3. CFF93 force field 4. AMBER 5. CHARMM (BIO+) 6. OPLS 7. ECEPP 8. The Merck force field (MMFF94) 9. Advantages and Disadvantages of the force field methods B. Solvation Effects in Molecular Mechanics 1. Introduction 2. Molecular solvent models 3. Continuum solvent models a. Surface area based b. Poisson-Boltzmann c. The GB/SA continuum model 4. Model comparison C. Minimization techniques 1. Simplex method

4 Course Outline Page 4 2. Line searching 3. Steepest descent 4. Conjugate gradient 5. Full matrix Newton-Raphson 6. Block diagonal Newton Raphson 7. Saddle Point search 8. Cerjan-Miller algorithm D. Conformational Analysis 1. Grid Search 2. Monte Carlo 3. Global minimum search 4. Macrocycles 5. Complexes & docking 6. Symmetry E. Binding Free Energy Calculation 1. Direct calculation 2. Calculation of Interaction Energies (Halgren s Method) 3. Multidimensional Monte Carlo integration F. Case Study(ies)/Applications 1. Conformational Analysis of substrate-macromolecule complexes 2. Deriving and using 3-dimensional pharmacophores 3. Structure-based methods to identify new lead compounds 4. De novo ligand design 5. Molecular similarity 6. QSAR VI. Combinatorial Chemistry (Sun) 4 lectures CC Chp 3. p51-97 Chp 7. p Chp 14. p A. Introduction: Concepts and Terms B. Solid-phase Strategies 1. General Strategies and Concepts 2. Specific Implementation Issues a. Solid support b. Anchoring chemistry c. Coupling chemistry d. Protection schemes e. Analytical methods C. Solution Phase Strategies D. High Throughput Screening

5 Course Outline Page 5 Reference Textbooks: BMC Burger s Medicinal Chemistry and Drug Discovery, 5th Edition, Vol. 1. Principles and Practice, edited by M. E. Wolff, John Wiley & Sons: New York, PMC Principles of Medicinal Chemistry, 4th Edition, edited by W.O. Foye, T.L. Lemke, and D. A. Williams, Williams and Wilkins: Philadelphia, MCPP Medicinal Chemistry: Principles and Practice, edited by F.D. King, Royal Society of Chemistry: Cambridge, CC A Practical Guide to Combinatorial Chemistry, edited by A. W. Czarnik and S. H. DeWitt, American Chemical Society: Washington DC, 1997.

Principles of Drug Design

Principles of Drug Design Advanced Medicinal Chemistry II Principles of Drug Design Tentative Course Outline Instructors: Longqin Hu and John Kerrigan Direct questions and enquiries to the Course Coordinator: Longqin Hu I. Introduction

More information

In silico pharmacology for drug discovery

In silico pharmacology for drug discovery In silico pharmacology for drug discovery In silico drug design In silico methods can contribute to drug targets identification through application of bionformatics tools. Currently, the application of

More information

CH MEDICINAL CHEMISTRY

CH MEDICINAL CHEMISTRY CH 458 - MEDICINAL CHEMISTRY SPRING 2011 M: 5:15pm-8 pm Sci-1-089 Prerequisite: Organic Chemistry II (Chem 254 or Chem 252, or equivalent transfer course) Instructor: Dr. Bela Torok Room S-1-132, Science

More information

Fondamenti di Chimica Farmaceutica. Computer Chemistry in Drug Research: Introduction

Fondamenti di Chimica Farmaceutica. Computer Chemistry in Drug Research: Introduction Fondamenti di Chimica Farmaceutica Computer Chemistry in Drug Research: Introduction Introduction Introduction Introduction Computer Chemistry in Drug Design Drug Discovery: Target identification Lead

More information

Early Stages of Drug Discovery in the Pharmaceutical Industry

Early Stages of Drug Discovery in the Pharmaceutical Industry Early Stages of Drug Discovery in the Pharmaceutical Industry Daniel Seeliger / Jan Kriegl, Discovery Research, Boehringer Ingelheim September 29, 2016 Historical Drug Discovery From Accidential Discovery

More information

FRAUNHOFER IME SCREENINGPORT

FRAUNHOFER IME SCREENINGPORT FRAUNHOFER IME SCREENINGPORT Design of screening projects General remarks Introduction Screening is done to identify new chemical substances against molecular mechanisms of a disease It is a question of

More information

Structural biology and drug design: An overview

Structural biology and drug design: An overview Structural biology and drug design: An overview livier Taboureau Assitant professor Chemoinformatics group-cbs-dtu otab@cbs.dtu.dk Drug discovery Drug and drug design A drug is a key molecule involved

More information

Introduction to Chemoinformatics and Drug Discovery

Introduction to Chemoinformatics and Drug Discovery Introduction to Chemoinformatics and Drug Discovery Irene Kouskoumvekaki Associate Professor February 15 th, 2013 The Chemical Space There are atoms and space. Everything else is opinion. Democritus (ca.

More information

ENERGY MINIMIZATION AND CONFORMATION SEARCH ANALYSIS OF TYPE-2 ANTI-DIABETES DRUGS

ENERGY MINIMIZATION AND CONFORMATION SEARCH ANALYSIS OF TYPE-2 ANTI-DIABETES DRUGS Int. J. Chem. Sci.: 6(2), 2008, 982-992 EERGY MIIMIZATI AD CFRMATI SEARC AALYSIS F TYPE-2 ATI-DIABETES DRUGS R. PRASAA LAKSMI a, C. ARASIMA KUMAR a, B. VASATA LAKSMI, K. AGA SUDA, K. MAJA, V. JAYA LAKSMI

More information

EMPIRICAL VS. RATIONAL METHODS OF DISCOVERING NEW DRUGS

EMPIRICAL VS. RATIONAL METHODS OF DISCOVERING NEW DRUGS EMPIRICAL VS. RATIONAL METHODS OF DISCOVERING NEW DRUGS PETER GUND Pharmacopeia Inc., CN 5350 Princeton, NJ 08543, USA pgund@pharmacop.com Empirical and theoretical approaches to drug discovery have often

More information

The University of Jordan

The University of Jordan The University of Jordan Faculty: Pharmacy Department: Pharmaceutical Sciences Program: Pharmacy and Pharm.D Academic 2013/ Fall Medicinal chemistry III (2152121) Credit hours 3 Level 3 Prerequisite Medicinal

More information

Ch 4: Cellular Metabolism, Part 1

Ch 4: Cellular Metabolism, Part 1 Developed by John Gallagher, MS, DVM Ch 4: Cellular Metabolism, Part 1 Energy as it relates to Biology Energy for synthesis and movement Energy transformation Enzymes and how they speed reactions Metabolism

More information

Receptor Based Drug Design (1)

Receptor Based Drug Design (1) Induced Fit Model For more than 100 years, the behaviour of enzymes had been explained by the "lock-and-key" mechanism developed by pioneering German chemist Emil Fischer. Fischer thought that the chemicals

More information

Quantitative structure activity relationship and drug design: A Review

Quantitative structure activity relationship and drug design: A Review International Journal of Research in Biosciences Vol. 5 Issue 4, pp. (1-5), October 2016 Available online at http://www.ijrbs.in ISSN 2319-2844 Research Paper Quantitative structure activity relationship

More information

Energy Transformation, Cellular Energy & Enzymes (Outline)

Energy Transformation, Cellular Energy & Enzymes (Outline) Energy Transformation, Cellular Energy & Enzymes (Outline) Energy conversions and recycling of matter in the ecosystem. Forms of energy: potential and kinetic energy The two laws of thermodynamic and definitions

More information

Docking. GBCB 5874: Problem Solving in GBCB

Docking. GBCB 5874: Problem Solving in GBCB Docking Benzamidine Docking to Trypsin Relationship to Drug Design Ligand-based design QSAR Pharmacophore modeling Can be done without 3-D structure of protein Receptor/Structure-based design Molecular

More information

TRAINING REAXYS MEDICINAL CHEMISTRY

TRAINING REAXYS MEDICINAL CHEMISTRY TRAINING REAXYS MEDICINAL CHEMISTRY 1 SITUATION: DRUG DISCOVERY Knowledge survey Therapeutic target Known ligands Generate chemistry ideas Chemistry Check chemical feasibility ELN DBs In-house Analyze

More information

RECENT TRENDS IN PHARMACEUTICAL CHEMISTRY FOR DRUG DISCOVERY

RECENT TRENDS IN PHARMACEUTICAL CHEMISTRY FOR DRUG DISCOVERY INTERNATIONAL JOURNAL OF RESEARCH IN PHARMACY AND CHEMISTRY Available online at www.ijrpc.com Review Article RECENT TRENDS IN PHARMACEUTICAL CHEMISTRY FOR DRUG DISCOVERY Sathyaraj A Department of Chemistry,

More information

Computational Chemistry in Drug Design. Xavier Fradera Barcelona, 17/4/2007

Computational Chemistry in Drug Design. Xavier Fradera Barcelona, 17/4/2007 Computational Chemistry in Drug Design Xavier Fradera Barcelona, 17/4/2007 verview Introduction and background Drug Design Cycle Computational methods Chemoinformatics Ligand Based Methods Structure Based

More information

CHEMISTRY (CHE) CHE 104 General Descriptive Chemistry II 3

CHEMISTRY (CHE) CHE 104 General Descriptive Chemistry II 3 Chemistry (CHE) 1 CHEMISTRY (CHE) CHE 101 Introductory Chemistry 3 Survey of fundamentals of measurement, molecular structure, reactivity, and organic chemistry; applications to textiles, environmental,

More information

Molecular Interactions F14NMI. Lecture 4: worked answers to practice questions

Molecular Interactions F14NMI. Lecture 4: worked answers to practice questions Molecular Interactions F14NMI Lecture 4: worked answers to practice questions http://comp.chem.nottingham.ac.uk/teaching/f14nmi jonathan.hirst@nottingham.ac.uk (1) (a) Describe the Monte Carlo algorithm

More information

Computational chemical biology to address non-traditional drug targets. John Karanicolas

Computational chemical biology to address non-traditional drug targets. John Karanicolas Computational chemical biology to address non-traditional drug targets John Karanicolas Our computational toolbox Structure-based approaches Ligand-based approaches Detailed MD simulations 2D fingerprints

More information

JCICS Major Research Areas

JCICS Major Research Areas JCICS Major Research Areas Chemical Information Text Searching Structure and Substructure Searching Databases Patents George W.A. Milne C571 Lecture Fall 2002 1 JCICS Major Research Areas Chemical Computation

More information

Molecular Dynamics Graphical Visualization 3-D QSAR Pharmacophore QSAR, COMBINE, Scoring Functions, Homology Modeling,..

Molecular Dynamics Graphical Visualization 3-D QSAR Pharmacophore QSAR, COMBINE, Scoring Functions, Homology Modeling,.. 3 Conformational Search Molecular Docking Simulate Annealing Ab Initio QM Molecular Dynamics Graphical Visualization 3-D QSAR Pharmacophore QSAR, COMBINE, Scoring Functions, Homology Modeling,.. Rino Ragno:

More information

Chapter 8: An Introduction to Metabolism

Chapter 8: An Introduction to Metabolism AP Biology Reading Guide Name Chapter 8: An Introduction to Metabolism Concept 8.1 An organism s metabolism transforms matter and energy, subject to the laws of thermodynamics 1. Define metabolism. 2.

More information

Structure-Based Drug Discovery An Overview

Structure-Based Drug Discovery An Overview Structure-Based Drug Discovery An Overview Edited by Roderick E. Hubbard University of York, Heslington, York, UK and Vernalis (R&D) Ltd, Abington, Cambridge, UK RSC Publishing Contents Chapter 1 3D Structure

More information

Retrieving hits through in silico screening and expert assessment M. N. Drwal a,b and R. Griffith a

Retrieving hits through in silico screening and expert assessment M. N. Drwal a,b and R. Griffith a Retrieving hits through in silico screening and expert assessment M.. Drwal a,b and R. Griffith a a: School of Medical Sciences/Pharmacology, USW, Sydney, Australia b: Charité Berlin, Germany Abstract:

More information

ENZYME KINETICS. Medical Biochemistry, Lecture 24

ENZYME KINETICS. Medical Biochemistry, Lecture 24 ENZYME KINETICS Medical Biochemistry, Lecture 24 Lecture 24, Outline Michaelis-Menten kinetics Interpretations and uses of the Michaelis- Menten equation Enzyme inhibitors: types and kinetics Enzyme Kinetics

More information

Science Textbook and Instructional Materials Correlation to the 2010 Biology Standards of Learning and Curriculum Framework. Publisher Information

Science Textbook and Instructional Materials Correlation to the 2010 Biology Standards of Learning and Curriculum Framework. Publisher Information Publisher Information Copyright date 2013 Contact Carol Kornfeind Phone# 847-486-2065 E-mail carol.kornfeind@pearson.com Biology 1 of 12 Virginia Department of Education Text Miller Levine Biology, Virginia

More information

Chapter 6~ An Introduction to Metabolism

Chapter 6~ An Introduction to Metabolism Chapter 6~ An Introduction to Metabolism Metabolism/Bioenergetics Metabolism: The totality of an organism s chemical processes; managing the material and energy resources of the cell Catabolic pathways:

More information

Molecular Mechanics, Dynamics & Docking

Molecular Mechanics, Dynamics & Docking Molecular Mechanics, Dynamics & Docking Lawrence Hunter, Ph.D. Director, Computational Bioscience Program University of Colorado School of Medicine Larry.Hunter@uchsc.edu http://compbio.uchsc.edu/hunter

More information

Dr. Sander B. Nabuurs. Computational Drug Discovery group Center for Molecular and Biomolecular Informatics Radboud University Medical Centre

Dr. Sander B. Nabuurs. Computational Drug Discovery group Center for Molecular and Biomolecular Informatics Radboud University Medical Centre Dr. Sander B. Nabuurs Computational Drug Discovery group Center for Molecular and Biomolecular Informatics Radboud University Medical Centre The road to new drugs. How to find new hits? High Throughput

More information

Ping-Chiang Lyu. Institute of Bioinformatics and Structural Biology, Department of Life Science, National Tsing Hua University.

Ping-Chiang Lyu. Institute of Bioinformatics and Structural Biology, Department of Life Science, National Tsing Hua University. Pharmacophore-based Drug design Ping-Chiang Lyu Institute of Bioinformatics and Structural Biology, Department of Life Science, National Tsing Hua University 96/08/07 Outline Part I: Analysis The analytical

More information

BOOK REVIEWS BY MANFRED E. WOLFF Wolff, M. E. (1970). "Hormonal Contraception." Journal of Medicinal Chemistry 13(5): 787-787. Wolff, M. E. (1996). "New Perspectives in Drug Design Edited by P. M. Dean,

More information

Syllabus BINF Computational Biology Core Course

Syllabus BINF Computational Biology Core Course Course Description Syllabus BINF 701-702 Computational Biology Core Course BINF 701/702 is the Computational Biology core course developed at the KU Center for Computational Biology. The course is designed

More information

Ignasi Belda, PhD CEO. HPC Advisory Council Spain Conference 2015

Ignasi Belda, PhD CEO. HPC Advisory Council Spain Conference 2015 Ignasi Belda, PhD CEO HPC Advisory Council Spain Conference 2015 Business lines Molecular Modeling Services We carry out computational chemistry projects using our selfdeveloped and third party technologies

More information

Bio 101 General Biology 1

Bio 101 General Biology 1 Revised: Fall 2016 Bio 101 General Biology 1 COURSE OUTLINE Prerequisites: Prerequisite: Successful completion of MTE 1, 2, 3, 4, and 5, and a placement recommendation for ENG 111, co-enrollment in ENF

More information

Development of Pharmacophore Model for Indeno[1,2-b]indoles as Human Protein Kinase CK2 Inhibitors and Database Mining

Development of Pharmacophore Model for Indeno[1,2-b]indoles as Human Protein Kinase CK2 Inhibitors and Database Mining Development of Pharmacophore Model for Indeno[1,2-b]indoles as Human Protein Kinase CK2 Inhibitors and Database Mining Samer Haidar 1, Zouhair Bouaziz 2, Christelle Marminon 2, Tiomo Laitinen 3, Anti Poso

More information

The Practice of Medicinal Chemistry

The Practice of Medicinal Chemistry A The Practice of Medicinal Chemistry Edited by CAMILLE G. WERMUTH Laboratoire de Pharmacochimie Moleculaire, Faculte de Pharmacie, Universite Louis Pasteur, Illkirch, France ACADEMIC PRESS Harcourt Brace

More information

Homology modeling. Dinesh Gupta ICGEB, New Delhi 1/27/2010 5:59 PM

Homology modeling. Dinesh Gupta ICGEB, New Delhi 1/27/2010 5:59 PM Homology modeling Dinesh Gupta ICGEB, New Delhi Protein structure prediction Methods: Homology (comparative) modelling Threading Ab-initio Protein Homology modeling Homology modeling is an extrapolation

More information

Keywords: anti-coagulants, factor Xa, QSAR, Thrombosis. Introduction

Keywords: anti-coagulants, factor Xa, QSAR, Thrombosis. Introduction PostDoc Journal Vol. 2, No. 3, March 2014 Journal of Postdoctoral Research www.postdocjournal.com QSAR Study of Thiophene-Anthranilamides Based Factor Xa Direct Inhibitors Preetpal S. Sidhu Department

More information

Drug Discovery. Zainab Al Kharusi Office: 33-10

Drug Discovery. Zainab Al Kharusi Office: 33-10 Drug Discovery Zainab Al Kharusi Office: 33-10 Objectives: To understand the processes of Drug Development To be able to develop a plan for drug discovery Reference: Patrick G L. An Introduction to Medicinal

More information

Introduction to FBDD Fragment screening methods and library design

Introduction to FBDD Fragment screening methods and library design Introduction to FBDD Fragment screening methods and library design Samantha Hughes, PhD Fragments 2013 RSC BMCS Workshop 3 rd March 2013 Copyright 2013 Galapagos NV Why fragment screening methods? Guess

More information

Plan. Day 2: Exercise on MHC molecules.

Plan. Day 2: Exercise on MHC molecules. Plan Day 1: What is Chemoinformatics and Drug Design? Methods and Algorithms used in Chemoinformatics including SVM. Cross validation and sequence encoding Example and exercise with herg potassium channel:

More information

Bioisosterism. A Rational Approach in Drug Design. 刘俊辉 Sept. 30th Sila-majantol 1b. lily-of-the-valley flowers but more terpineol-like odor

Bioisosterism. A Rational Approach in Drug Design. 刘俊辉 Sept. 30th Sila-majantol 1b. lily-of-the-valley flowers but more terpineol-like odor Bioisosterism A Rational Approach in Drug Design 刘俊辉 Sept. 30th 2005 Why is Bioisosterism? Me C 2 C Me Majantol 1a strong fresh-floral aqueousaldehydic, lily-of-the-valley flowers odor Me C 2 Si Me Sila-majantol

More information

Structure based drug design and LIE models for GPCRs

Structure based drug design and LIE models for GPCRs Structure based drug design and LIE models for GPCRs Peter Kolb kolb@docking.org Shoichet Lab ACS 237 th National Meeting, March 24, 2009 p.1/26 [Acknowledgements] Brian Shoichet John Irwin Mike Keiser

More information

A primer on pharmacology pharmacodynamics

A primer on pharmacology pharmacodynamics A primer on pharmacology pharmacodynamics Drug binding & effect Universidade do Algarve Faro 2017 by Ferdi Engels, Ph.D. 1 Pharmacodynamics Relation with pharmacokinetics? dosage plasma concentration site

More information

Biological Pathways Representation by Petri Nets and extension

Biological Pathways Representation by Petri Nets and extension Biological Pathways Representation by and extensions December 6, 2006 Biological Pathways Representation by and extension 1 The cell Pathways 2 Definitions 3 4 Biological Pathways Representation by and

More information

Introduction. OntoChem

Introduction. OntoChem Introduction ntochem Providing drug discovery knowledge & small molecules... Supporting the task of medicinal chemistry Allows selecting best possible small molecule starting point From target to leads

More information

5.1. Hardwares, Softwares and Web server used in Molecular modeling

5.1. Hardwares, Softwares and Web server used in Molecular modeling 5. EXPERIMENTAL The tools, techniques and procedures/methods used for carrying out research work reported in this thesis have been described as follows: 5.1. Hardwares, Softwares and Web server used in

More information

Molecular Simulation II. Classical Mechanical Treatment

Molecular Simulation II. Classical Mechanical Treatment Molecular Simulation II Quantum Chemistry Classical Mechanics E = Ψ H Ψ ΨΨ U = E bond +E angle +E torsion +E non-bond Jeffry D. Madura Department of Chemistry & Biochemistry Center for Computational Sciences

More information

pharmaceutical industry- drug discovery

pharmaceutical industry- drug discovery ombinatorial hemistry: molecular diversity "Synthesis and pplications of Small Molecule Libraries." Thompson, L..; llman, J.. hem. ev.,, -00. "esign, Synthesis, and valuation of Small-Molecule Libraries.

More information

Protein structure based approaches to inhibit Plasmodium DHODH for malaria

Protein structure based approaches to inhibit Plasmodium DHODH for malaria Protein structure based approaches to inhibit Plasmodium DHDH for malaria Peter Johnson University of Leeds, School of Chemistry email p.johnson@leeds.ac.uk Tools for protein structure based approaches

More information

Enzyme Enzymes are proteins that act as biological catalysts. Enzymes accelerate, or catalyze, chemical reactions. The molecules at the beginning of

Enzyme Enzymes are proteins that act as biological catalysts. Enzymes accelerate, or catalyze, chemical reactions. The molecules at the beginning of Enzyme Enzyme Enzymes are proteins that act as biological catalysts. Enzymes accelerate, or catalyze, chemical reactions. The molecules at the beginning of the process are called substrates and the enzyme

More information

STRUCTURAL BIOINFORMATICS II. Spring 2018

STRUCTURAL BIOINFORMATICS II. Spring 2018 STRUCTURAL BIOINFORMATICS II Spring 2018 Syllabus Course Number - Classification: Chemistry 5412 Class Schedule: Monday 5:30-7:50 PM, SERC Room 456 (4 th floor) Instructors: Ronald Levy, SERC 718 (ronlevy@temple.edu)

More information

Characterization of Reversible Kinase Inhibitors using Microfluidic Mobility-Shift Assays

Characterization of Reversible Kinase Inhibitors using Microfluidic Mobility-Shift Assays Application Note 211 Characterization of Reversible Kinase Inhibitors using Microfluidic Mobility-Shift Assays Introduction Current drug discovery efforts typically focus on developing small molecule inhibitors

More information

Course Specification Medicinal Chemistry-1

Course Specification Medicinal Chemistry-1 Quality Assurance Unit Faculty of Pharmacy-Assiut University Course Specification Medicinal Chemistry-1 Programme(s) on which the course is given: B. Sc. (Pharmaceutical science) Major or Minor element

More information

Chapter 6 Active Reading Guide An Introduction to Metabolism

Chapter 6 Active Reading Guide An Introduction to Metabolism Name: AP Biology Mr. Croft Section 1 1. Define metabolism. Chapter 6 Active Reading Guide An Introduction to Metabolism 2. There are two types of reactions in metabolic pathways: anabolic and catabolic.

More information

Medicinal Chemistry 1

Medicinal Chemistry 1 Medicinal Chemistry 1 1-Basic Information Title: Medicinal Chemistry 1 Code: PHC - 415 Level: Third year (1 st Semester) Department: Medicinal Chemistry Unit: Lecture: 2(2hrs) Tutorial/ Practical:1(3hrs)

More information

BCMB 3100 Chapters 6,7,8 Enzyme Basics. Six Classes (IUBMB) Kinetics Michaelis-Menten Equation Vo, Km, Vmax, Kcat Lineweaver-Burk Plot

BCMB 3100 Chapters 6,7,8 Enzyme Basics. Six Classes (IUBMB) Kinetics Michaelis-Menten Equation Vo, Km, Vmax, Kcat Lineweaver-Burk Plot BCMB 3100 Chapters 6,7,8 Enzyme Basics Six Classes (IUBMB) Kinetics Enzymes are biological macromolecules that increase the rate of the reaction. Six major groups of enzymes (pgs. 94-95/98-99) Oxidoreductases:

More information

CHEM 4170 Problem Set #1

CHEM 4170 Problem Set #1 CHEM 4170 Problem Set #1 0. Work problems 1-7 at the end of Chapter ne and problems 1, 3, 4, 5, 8, 10, 12, 17, 18, 19, 22, 24, and 25 at the end of Chapter Two and problem 1 at the end of Chapter Three

More information

Virtual screening in drug discovery

Virtual screening in drug discovery Virtual screening in drug discovery Pavel Polishchuk Institute of Molecular and Translational Medicine Palacky University pavlo.polishchuk@upol.cz Drug development workflow Vistoli G., et al., Drug Discovery

More information

RATIONAL DRUG DESIGN

RATIONAL DRUG DESIGN RATIOAL DRUG DESIG Drug Design & Discovery: Introduction Drugs: Targets: atural sources Synthetic sources Ideal Drug 1) target: bio-molecule,involved in signaling or metabolic pathways, that are specific

More information

Virginia Western Community College BIO 101 General Biology I

Virginia Western Community College BIO 101 General Biology I BIO 101 General Biology I Prerequisites Successful completion of MTE 1, 2, 3, 4, and 5; and a placement recommendation for ENG 111, co-enrollment in ENF 3/ENG 111, or successful completion of all developmental

More information

BCMB 3100 Chapters 6,7,8 Enzyme Basics. Six Classes (IUBMB) Kinetics Michaelis-Menten Equation Vo, Km, Vmax, Kcat Lineweaver-Burk Plot

BCMB 3100 Chapters 6,7,8 Enzyme Basics. Six Classes (IUBMB) Kinetics Michaelis-Menten Equation Vo, Km, Vmax, Kcat Lineweaver-Burk Plot BCMB 3100 Chapters 6,7,8 Enzyme Basics Six Classes (IUBMB) Kinetics Michaelis-Menten Equation Vo, Km, Vmax, Kcat Lineweaver-Burk Plot Enzymes are biological macromolecules that increase the rate of the

More information

BCMB 3100 Chapters 6,7,8 Enzyme Basics. Six Classes (IUBMB) Kinetics Michaelis-Menten Equation Vo, Km, Vmax, Kcat Lineweaver-Burk Plot

BCMB 3100 Chapters 6,7,8 Enzyme Basics. Six Classes (IUBMB) Kinetics Michaelis-Menten Equation Vo, Km, Vmax, Kcat Lineweaver-Burk Plot BCMB 3100 Chapters 6,7,8 Enzyme Basics Six Classes (IUBMB) Kinetics Michaelis-Menten Equation Vo, Km, Vmax, Kcat Lineweaver-Burk Plot Enzymes are biological macromolecules that increase the rate of the

More information

Structural Bioinformatics (C3210) Molecular Docking

Structural Bioinformatics (C3210) Molecular Docking Structural Bioinformatics (C3210) Molecular Docking Molecular Recognition, Molecular Docking Molecular recognition is the ability of biomolecules to recognize other biomolecules and selectively interact

More information

Previous Class. Today. Cosubstrates (cofactors)

Previous Class. Today. Cosubstrates (cofactors) Previous Class Cosubstrates (cofactors) Today Proximity effect Basic equations of Kinetics Steady state kinetics Michaelis Menten equations and parameters Enzyme Kinetics Enzyme kinetics implies characterizing

More information

Chapter 8: An Introduction to Metabolism

Chapter 8: An Introduction to Metabolism Chapter 8: An Introduction to Metabolism Name Period Concept 8.1 An organism s metabolism transforms matter and energy, subject to the laws of thermodynamics 1. Define metabolism. 2. There are two types

More information

Author Index Volume

Author Index Volume Perspectives in Drug Discovery and Design, 20: 289, 2000. KLUWER/ESCOM Author Index Volume 20 2000 Bradshaw,J., 1 Knegtel,R.M.A., 191 Rose,P.W., 209 Briem, H., 231 Kostka, T., 245 Kuhn, L.A., 171 Sadowski,

More information

SIMPLE MODEL Direct Binding Analysis

SIMPLE MODEL Direct Binding Analysis Neurochemistry, 56:120:575 Dr. Patrick J. McIlroy Supplementary Notes SIMPLE MODEL Direct Binding Analysis The interaction of a (radio)ligand, L, with its receptor, R, to form a non-covalent complex, RL,

More information

MM-GBSA for Calculating Binding Affinity A rank-ordering study for the lead optimization of Fxa and COX-2 inhibitors

MM-GBSA for Calculating Binding Affinity A rank-ordering study for the lead optimization of Fxa and COX-2 inhibitors MM-GBSA for Calculating Binding Affinity A rank-ordering study for the lead optimization of Fxa and COX-2 inhibitors Thomas Steinbrecher Senior Application Scientist Typical Docking Workflow Databases

More information

COMBINATORIAL CHEMISTRY: CURRENT APPROACH

COMBINATORIAL CHEMISTRY: CURRENT APPROACH COMBINATORIAL CHEMISTRY: CURRENT APPROACH Dwivedi A. 1, Sitoke A. 2, Joshi V. 3, Akhtar A.K. 4* and Chaturvedi M. 1, NRI Institute of Pharmaceutical Sciences, Bhopal, M.P.-India 2, SRM College of Pharmacy,

More information

Course Plan (Syllabus): Drug Design and Discovery

Course Plan (Syllabus): Drug Design and Discovery Course Plan (Syllabus): Drug Design and Discovery (A) Course Identification and General Information Course Number & Code PPC 515 Course Title Drug Design and Discovery (Elective course) Program (s) in

More information

György M. Keserű H2020 FRAGNET Network Hungarian Academy of Sciences

György M. Keserű H2020 FRAGNET Network Hungarian Academy of Sciences Fragment based lead discovery - introduction György M. Keserű H2020 FRAGET etwork Hungarian Academy of Sciences www.fragnet.eu Hit discovery from screening Druglike library Fragment library Large molecules

More information

Science Online Instructional Materials Correlation to the 2010 Biology Standards of Learning and Curriculum Framework

Science Online Instructional Materials Correlation to the 2010 Biology Standards of Learning and Curriculum Framework and Curriculum Framework Provider York County School Divison Course Title Biology Last Updated 2010-11 Course Syllabus URL http://yorkcountyschools.org/virtuallearning/coursecatalog.aspx BIO.1 The student

More information

PHARMACOKINETIC DERIVATION OF RATES AND ORDERS OF REACTIONS IN MULTI- COMPARTMENT MODEL USING MATLAB

PHARMACOKINETIC DERIVATION OF RATES AND ORDERS OF REACTIONS IN MULTI- COMPARTMENT MODEL USING MATLAB IJPSR (2016), Vol. 7, Issue 11 (Research Article) Received on 29 May, 2016; received in revised form, 07 July, 2016; accepted, 27 July, 2016; published 01 November, 2016 PHARMACOKINETIC DERIVATION OF RATES

More information

ENZYMES. by: Dr. Hadi Mozafari

ENZYMES. by: Dr. Hadi Mozafari ENZYMES by: Dr. Hadi Mozafari 1 Specifications Often are Polymers Have a protein structures Enzymes are the biochemical reactions Katalyzers Enzymes are Simple & Complex compounds 2 Enzymatic Reactions

More information

Chemogenomic: Approaches to Rational Drug Design. Jonas Skjødt Møller

Chemogenomic: Approaches to Rational Drug Design. Jonas Skjødt Møller Chemogenomic: Approaches to Rational Drug Design Jonas Skjødt Møller Chemogenomic Chemistry Biology Chemical biology Medical chemistry Chemical genetics Chemoinformatics Bioinformatics Chemoproteomics

More information

Synthetic organic compounds

Synthetic organic compounds Synthetic organic compounds for research and drug discovery Compounds for TS Fragment libraries Target-focused libraries Chemical building blocks Custom synthesis Drug discovery services Contract research

More information

Chapter 8: An Introduction to Metabolism

Chapter 8: An Introduction to Metabolism Chapter 8: An Introduction to Metabolism Key Concepts 8.1 An organism s metabolism transforms matter and energy, subject to the laws of thermodynamics 8.2 The free-energy change of a reaction tells us

More information

Softwares for Molecular Docking. Lokesh P. Tripathi NCBS 17 December 2007

Softwares for Molecular Docking. Lokesh P. Tripathi NCBS 17 December 2007 Softwares for Molecular Docking Lokesh P. Tripathi NCBS 17 December 2007 Molecular Docking Attempt to predict structures of an intermolecular complex between two or more molecules Receptor-ligand (or drug)

More information

k -2 k 2 K F I-N k 3 k -1 K F U-I k 1 NSP

k -2 k 2 K F I-N k 3 k -1 K F U-I k 1 NSP Symposium on Protein Misfolding Diseases Biochemistry & Molecular Biology website May 1-2, 2007 University of Massachusetts Amherst Tuesday, May 1 1:00-1:30pm Registration 1:30-3:30pm Panel discussion:

More information

Data Quality Issues That Can Impact Drug Discovery

Data Quality Issues That Can Impact Drug Discovery Data Quality Issues That Can Impact Drug Discovery Sean Ekins 1, Joe Olechno 2 Antony J. Williams 3 1 Collaborations in Chemistry, Fuquay Varina, NC. 2 Labcyte Inc, Sunnyvale, CA. 3 Royal Society of Chemistry,

More information

2013 W. H. Freeman and Company. 6 Enzymes

2013 W. H. Freeman and Company. 6 Enzymes 2013 W. H. Freeman and Company 6 Enzymes CHAPTER 6 Enzymes Key topics about enzyme function: Physiological significance of enzymes Origin of catalytic power of enzymes Chemical mechanisms of catalysis

More information

Chemistry 1506: Allied Health Chemistry 2. Section 10: Enzymes. Biochemical Catalysts. Outline

Chemistry 1506: Allied Health Chemistry 2. Section 10: Enzymes. Biochemical Catalysts. Outline Chemistry 1506 Dr. Hunter s Class Section 10 Notes - Page 1/14 Chemistry 1506: Allied Health Chemistry 2 Section 10: Enzymes Biochemical Catalysts. Outline SECTION 10.1 INTRODUCTION...2 SECTION SECTION

More information

Chapter 8. Enzymes: basic concept and kinetics

Chapter 8. Enzymes: basic concept and kinetics Chapter 8 Enzymes: basic concept and kinetics Learning objectives: mechanism of enzymatic catalysis Michaelis -Menton Model Inhibition Single Molecule of Enzymatic Reaction Enzymes: catalysis chemical

More information

Dispensing Processes Profoundly Impact Biological, Computational and Statistical Analyses

Dispensing Processes Profoundly Impact Biological, Computational and Statistical Analyses Dispensing Processes Profoundly Impact Biological, Computational and Statistical Analyses Sean Ekins 1, Joe Olechno 2 Antony J. Williams 3 1 Collaborations in Chemistry, Fuquay Varina, NC. 2 Labcyte Inc,

More information

Metabolism: Energy and Enzymes. February 24 th, 2012

Metabolism: Energy and Enzymes. February 24 th, 2012 Metabolism: Energy and Enzymes February 24 th, 2012 1 Outline Forms of Energy Laws of Thermodynamics Metabolic Reactions ATP Metabolic Pathways Energy of Activation Enzymes Photosynthesis Cellular Respiration

More information

Chapter 8: An Introduction to Metabolism

Chapter 8: An Introduction to Metabolism Name Period Concept 8.1 An organism s metabolism transforms matter and energy, subject to the laws of thermodynamics 1. Define metabolism. 2. There are two types of reactions in metabolic pathways: anabolic

More information

Title: Medicinal Chemistry 3

Title: Medicinal Chemistry 3 Medicinal Chemistry 3 1-Basic Information Title: Medicinal Chemistry 3 Code: PHC-515 Level: Fourth year (1 st Semester) Department: Medicinal Chemistry Unit: Lecture:2(2hrs) Tutorial/ Practical:1(3 hrs)

More information

Cheminformatics platform for drug discovery application

Cheminformatics platform for drug discovery application EGI-InSPIRE Cheminformatics platform for drug discovery application Hsi-Kai, Wang Academic Sinica Grid Computing EGI User Forum, 13, April, 2011 1 Introduction to drug discovery Computing requirement of

More information

Welcome to Week 5. Chapter 9 - Binding, Structure, and Diversity. 9.1 Intermolecular Forces. Starting week five video. Introduction to Chapter 9

Welcome to Week 5. Chapter 9 - Binding, Structure, and Diversity. 9.1 Intermolecular Forces. Starting week five video. Introduction to Chapter 9 Welcome to Week 5 Starting week five video Please watch the online video (49 seconds). Chapter 9 - Binding, Structure, and Diversity Introduction to Chapter 9 Chapter 9 contains six subsections. Intermolecular

More information

COMPUTER AIDED DRUG DESIGN (CADD) AND DEVELOPMENT METHODS

COMPUTER AIDED DRUG DESIGN (CADD) AND DEVELOPMENT METHODS COMPUTER AIDED DRUG DESIGN (CADD) AND DEVELOPMENT METHODS DRUG DEVELOPMENT Drug development is a challenging path Today, the causes of many diseases (rheumatoid arthritis, cancer, mental diseases, etc.)

More information

Introduction to medicinal chemisry

Introduction to medicinal chemisry 2017 1 st edition Introduction to medicinal chemisry Med Chem I Mohammed Nooraldeen (PhD) كيمياء دوائية )1 ) محمد نورالدين محمود Introduction to medicinal chemistry Medicinal Chemistry Biology Medicine

More information

Virtual Screening: How Are We Doing?

Virtual Screening: How Are We Doing? Virtual Screening: How Are We Doing? Mark E. Snow, James Dunbar, Lakshmi Narasimhan, Jack A. Bikker, Dan Ortwine, Christopher Whitehead, Yiannis Kaznessis, Dave Moreland, Christine Humblet Pfizer Global

More information

THE RELATIONSHIP BETWEEN NATURAL PRODUCTS AND SYNTHETIC. Poldhune Parc Owles, Carbis Bay, St. Ives, Cornwall TR26 2RE, UK.

THE RELATIONSHIP BETWEEN NATURAL PRODUCTS AND SYNTHETIC. Poldhune Parc Owles, Carbis Bay, St. Ives, Cornwall TR26 2RE, UK. THE RELATIONSHIP BETWEEN NATURAL PRODUCTS AND SYNTHETIC CHEMISTRY IN THE DISCOVERY PROCESS by Dr. Stephen Brewer Consultant, Bioproducts Technology Poldhune Parc Owles, Carbis Bay, St. Ives, Cornwall TR26

More information

Michaelis Menten Kinetics- Identical Independent Binding Sites

Michaelis Menten Kinetics- Identical Independent Binding Sites Michaelis Menten Kinetics- Identical Independent Binding Sites Dr. M. Vijayalakshmi School of Chemical and Biotechnology SASTRA University Joint Initiative of IITs and IISc Funded by MHRD Page 1 of 8 Table

More information

Enzyme Kinetics. Differential Equations Series. Instructor s Guide. Table of Contents

Enzyme Kinetics. Differential Equations Series. Instructor s Guide. Table of Contents Enzyme Kinetics Differential Equations Series Instructor s Guide Table of Contents Introduction.... 2 When to Use this Video.... 2 Learning Objectives.... 2 Motivation.... 2 Student Experience.... 2 Key

More information

Progress of Compound Library Design Using In-silico Approach for Collaborative Drug Discovery

Progress of Compound Library Design Using In-silico Approach for Collaborative Drug Discovery 21 th /June/2018@CUGM Progress of Compound Library Design Using In-silico Approach for Collaborative Drug Discovery Kaz Ikeda, Ph.D. Keio University Self Introduction Keio University, Tokyo, Japan (Established

More information