Protein Folding & Stability. Lecture 11: Margaret A. Daugherty. Fall How do we go from an unfolded polypeptide chain to a

Size: px
Start display at page:

Download "Protein Folding & Stability. Lecture 11: Margaret A. Daugherty. Fall How do we go from an unfolded polypeptide chain to a"

Transcription

1 Lecture 11: Protein Folding & Stability Margaret A. Daugherty Fall 2004 How do we go from an unfolded polypeptide chain to a compact folded protein? (Folding of thioredoxin, F. Richards)

2 Structure - Function Protein Folding: What we know 1). Amino acid sequence dictates structure. 2). The native structure represents the lowest energy state for a protein (physiological conditions). 3). Proteins are densely packed as small organic crystals. Protein Folding 4). A protein cannot sample all possible conformations in finding its native structure (Levinthal s paradox). 5). Protein folding in vitro is a good model for in vivo folding. 6). Protein folding is a cooperative process, usually between N <--> U states. 7). Intermediates with non-native structure can exist is some protein folding pathways. 8). The molten globule is likely to be an intermediate on protein folding pathways. The Future of Folding 9). The protein folding problem will be solved within 5 years (Walter Gilbert, 1988) 10). Designed proteins usually turn out to be molten globules. 11). We will eventually be able to predict protein structure from sequence. Anfinsen s protein folding experiment Ribonuclease A 124 aa, pancreatic enzyme

3 Anfinsen s experiment: sequence dictates structure `57: Nobel Prize in 1972 (1) a. Reduce protein (β-me destroys disulfides) b, Unfold protein in urea (2) Remove urea - allow protein to refold Remove β-me- allow disulfide to reoxidize (1) 100 % activity (2) (4) ~1% activity (3) Remove β-me - allow disulfides to reoxidize Remove urea - alllow protein to refold (4) Add trace β-me, warm ~10 hrs ==> 100% ACTIVITY Add trace β-me + cytosolic* fraction ~2 minutes ==>100% ACTIVITY 0% activity (3) Protein folding Thermodynamic component: The native structure represents the lowest energy state for a protein Kinetic component: A protein cannot sample all possible conformations in finding its native structure

4 PROTEIN FOLDING IS ENERGETICALLY FAVORABLE Unfavorable (more positive) Free Energy Favorable (more negative) Unfolded Nucleation of secondary structural elements Interaction of secondary structural elements molten globule? Native Energetic contributions to protein folding Conformational entropy Hydrogen bonds Electrostatic Forces *The hydrophobic effect* van der Waals Forces Other forces

5 CONFORMATIONAL ENTROPY Boltzmann s Equation: S = k ln W VS. The polypeptide chain in the unfolded state has more conformational freedom than the folded state. Thus, the conformational entropy is a destabilizing component of the native state free energy HYDROPHOBIC EFFECT Hydrophobic effect: Thermodynamic consequence due to avoidance of H 2 0 by the apolar side chains of a protein. Predicted in 1959 by Kauzmann (before 3D structures). Major contributor to stabilization of native state: proportional to apolar surface area buried.

6 ordered H 2 0 about hydrophobes result in clathrate structures Entropically unfavorable Sequestering of hydrophobes to interior of protein molecule => Release of H 2 0 is ENTROPICALLY FAVORABLE HYDROGEN BONDS IN PROTEINS Almost all groups capable of hydrogen bonding are, in fact, hydrogen bonded Baker & Hubbard, 1984

7 H-bond contribution to native state free energy may be small. Unfolded Folded H + H-O-H 0-H Stabilizing force only if protein-protein and water-water H-bonds are more favorable than those of protein-water ELECTROSTATIC FORCES Charge-charge ion pairs Charge-dipole amide-helix dipole helix-helix ion-helix Charge-dipole: U qm = qmcosθ/εr 2 m = dipole moment ε = dielectric constant

8 van der Waals Forces: non-polar interactions or dispersion forces: due to local fluctuations in electron density Electronic motion produces an electrostatic attraction U = A/r 12 - B/r 6 r Repulsive potential due to bringing two atoms so close that their electron clouds interpenetrate Attractive potential due to mutual induction of electrostatic dipoles. These attractive forces are weak. However, they are additive and can make a significant contribution to stability when summed over a molecule BPTI: bovine pancreatic trypsin inhibitor Folding Also Involves Arrangement of S-S bonds

9 Contributions to the native state free energy For a typical small globular proteins, the favorable and unfavorable interactions are energetically enormous (~100s kcal/mol) but the difference in free energy from unfolded to native state: G fold ~ -5 to - 10 kcal/mol KINETIC COMPONENT: LEVINTHAL S PARADOX AND TIME Given an polypeptide sequence, how does it fold into a native conformation in a reasonable amount of time? Example of ribonuclease (124 amino acid residues): if we assume each residue can sample 3 conformations ~10 50 conformations If folding samples a new conformation every seconds years to sample all conformations In vitro: ribonuclease folds in ~1-2 minutes

10 Many potential ways for a protein to fold Single path; one transition state Single path; multiple transition states Multiple paths; one transition state The native structure of a protein represents its lowest energy state The energy landscape of protein folding can be visualized as a funnel in which many paths to the lowest energy state, e.g., the folded state are possible. The paths through the funnel represent kinetic pathways. A. Rapid folding pathway B. Protein goes through an energy minimum, which may slow folding. unfolded folded ENERGY DECREASE entropy molten globule native state

11 IS PROTEIN FOLDING IN VITRO A GOOD MODEL FOR PROTEIN FOLDING IN VIVO? PARADOXES OF PROTEIN FOLDING: RATES OF CORRECT FOLDING: in vivo: few minutes in vitro: several hours EFFICIENCY OF CORRECT FOLDING: in vivo: ~ 99% in vitro: a few % for many OFTEN, in vitro REFOLDING OF POLYPEPTIDE CHAIN DOES NOT RESULT IN NATIVE STRUCTURE ACCESSORY PROTEINS PLAY AN IMPORTANT ROLE IN NASCENT PROTEIN FOLDING Conceptual transition from self-assembly to assisted assembly principle of protein folding Chaperone: assist in the correct non-covalent folding & assembly of nascent peptides. Chaperones manipulate the target conformation and are catalytic.

12 CHAPERONES: GroEL-GroES complex GroEL: 2 ring structure of 7 subunits GroES: ring structure with 7 subunits GroEL-GroES: STRUCTURAL CONSIDERATIONS GroES interaction alters conformation of the GroEL subunit, resulting in a correspondingly larger binding cavity Cavity limits: 80A 52 kd protein

13 GroEL 1). Non-native protein binds to the trans ring of GroEL-GroES complex. GroEL-GroES MECHANISM GroES 2). End-to-end exchange of GroES (through symmetric intermediate?). Substrate encapsulated in trans cavity. 3). In presence of ATP- productive folding of substrate protein occurs. trans 4). Release of GroES and native protein. GroEL-GroES complex is regenerated for next cycle. cis NOT ALL PROTEINS ARE STRUCTURED!

14 What is Levinthal s paradox? What does a folding funnel describe? Review What is the sequence of protein folding? What is a molten globule? What are the enthalpic and entropic contributions to protein folding? Is protein folding in vitro a good model for understanding in vivo folding? What are the two classes of accessory proteins involved in protein folding? How does GroEL-GroES mediate protein folding? How is the MW of a protein determined?

Lecture 11: Protein Folding & Stability

Lecture 11: Protein Folding & Stability Structure - Function Protein Folding: What we know Lecture 11: Protein Folding & Stability 1). Amino acid sequence dictates structure. 2). The native structure represents the lowest energy state for a

More information

Protein Folding & Stability. Lecture 11: Margaret A. Daugherty. Fall Protein Folding: What we know. Protein Folding

Protein Folding & Stability. Lecture 11: Margaret A. Daugherty. Fall Protein Folding: What we know. Protein Folding Lecture 11: Protein Folding & Stability Margaret A. Daugherty Fall 2003 Structure - Function Protein Folding: What we know 1). Amino acid sequence dictates structure. 2). The native structure represents

More information

The protein folding problem consists of two parts:

The protein folding problem consists of two parts: Energetics and kinetics of protein folding The protein folding problem consists of two parts: 1)Creating a stable, well-defined structure that is significantly more stable than all other possible structures.

More information

Energetics and Thermodynamics

Energetics and Thermodynamics DNA/Protein structure function analysis and prediction Protein Folding and energetics: Introduction to folding Folding and flexibility (Ch. 6) Energetics and Thermodynamics 1 Active protein conformation

More information

Biochemistry: Concepts and Connections

Biochemistry: Concepts and Connections Biochemistry: Concepts and Connections Dean R. Appling Spencer J. Anthony-Cahill Christopher K. Mathews Chapter 6 The Three Dimensional Structure of Proteins Cartoon representation of myoglobin, showing

More information

Protein Folding. I. Characteristics of proteins. C α

Protein Folding. I. Characteristics of proteins. C α I. Characteristics of proteins Protein Folding 1. Proteins are one of the most important molecules of life. They perform numerous functions, from storing oxygen in tissues or transporting it in a blood

More information

Protein folding. Today s Outline

Protein folding. Today s Outline Protein folding Today s Outline Review of previous sessions Thermodynamics of folding and unfolding Determinants of folding Techniques for measuring folding The folding process The folding problem: Prediction

More information

Protein Folding experiments and theory

Protein Folding experiments and theory Protein Folding experiments and theory 1, 2,and 3 Protein Structure Fig. 3-16 from Lehninger Biochemistry, 4 th ed. The 3D structure is not encoded at the single aa level Hydrogen Bonding Shared H atom

More information

Why Proteins Fold. How Proteins Fold? e - ΔG/kT. Protein Folding, Nonbonding Forces, and Free Energy

Why Proteins Fold. How Proteins Fold? e - ΔG/kT. Protein Folding, Nonbonding Forces, and Free Energy Why Proteins Fold Proteins are the action superheroes of the body. As enzymes, they make reactions go a million times faster. As versatile transport vehicles, they carry oxygen and antibodies to fight

More information

Lecture 21 (11/3/17) Protein Stability, Folding, and Dynamics Hydrophobic effect drives protein folding

Lecture 21 (11/3/17) Protein Stability, Folding, and Dynamics Hydrophobic effect drives protein folding Reading: Ch4; 142-151 Problems: Ch4 (text); 14, 16 Ch6 (text); 1, 4 NEXT (after exam) Reading: Ch8; 310-312, 279-285, 285-289 Ch24; 957-961 Problems: Ch8 (text); 1,2,22 Ch8 (study-guide:facts); 1,2,3,4,5,9,10

More information

BCHS 6229 Protein Structure and Function. Lecture 3 (October 18, 2011) Protein Folding: Forces, Mechanisms & Characterization

BCHS 6229 Protein Structure and Function. Lecture 3 (October 18, 2011) Protein Folding: Forces, Mechanisms & Characterization BCHS 6229 Protein Structure and Function Lecture 3 (October 18, 2011) Protein Folding: Forces, Mechanisms & Characterization 1 The folding problem One of the greatest unsolved problems of Science The folding

More information

Molecular Modelling. part of Bioinformatik von RNA- und Proteinstrukturen. Sonja Prohaska. Leipzig, SS Computational EvoDevo University Leipzig

Molecular Modelling. part of Bioinformatik von RNA- und Proteinstrukturen. Sonja Prohaska. Leipzig, SS Computational EvoDevo University Leipzig part of Bioinformatik von RNA- und Proteinstrukturen Computational EvoDevo University Leipzig Leipzig, SS 2011 Protein Structure levels or organization Primary structure: sequence of amino acids (from

More information

Quiz 2 Morphology of Complex Materials

Quiz 2 Morphology of Complex Materials 071003 Quiz 2 Morphology of Complex Materials 1) Explain the following terms: (for states comment on biological activity and relative size of the structure) a) Native State b) Unfolded State c) Denatured

More information

Flexibility of Protein Structure

Flexibility of Protein Structure Flexibility of Protein Structure Proteins show varying degree of conformational flexibility Due to movements of atoms in molecules vibration in bond length and angles Reflects the existence of populations

More information

Protein Structure. W. M. Grogan, Ph.D. OBJECTIVES

Protein Structure. W. M. Grogan, Ph.D. OBJECTIVES Protein Structure W. M. Grogan, Ph.D. OBJECTIVES 1. Describe the structure and characteristic properties of typical proteins. 2. List and describe the four levels of structure found in proteins. 3. Relate

More information

Many proteins spontaneously refold into native form in vitro with high fidelity and high speed.

Many proteins spontaneously refold into native form in vitro with high fidelity and high speed. Macromolecular Processes 20. Protein Folding Composed of 50 500 amino acids linked in 1D sequence by the polypeptide backbone The amino acid physical and chemical properties of the 20 amino acids dictate

More information

= (-22) = +2kJ /mol

= (-22) = +2kJ /mol Lecture 8: Thermodynamics & Protein Stability Assigned reading in Campbell: Chapter 4.4-4.6 Key Terms: DG = -RT lnk eq = DH - TDS Transition Curve, Melting Curve, Tm DH calculation DS calculation van der

More information

Lecture 2 and 3: Review of forces (ctd.) and elementary statistical mechanics. Contributions to protein stability

Lecture 2 and 3: Review of forces (ctd.) and elementary statistical mechanics. Contributions to protein stability Lecture 2 and 3: Review of forces (ctd.) and elementary statistical mechanics. Contributions to protein stability Part I. Review of forces Covalent bonds Non-covalent Interactions: Van der Waals Interactions

More information

4 Proteins: Structure, Function, Folding W. H. Freeman and Company

4 Proteins: Structure, Function, Folding W. H. Freeman and Company 4 Proteins: Structure, Function, Folding 2013 W. H. Freeman and Company CHAPTER 4 Proteins: Structure, Function, Folding Learning goals: Structure and properties of the peptide bond Structural hierarchy

More information

Proteins are not rigid structures: Protein dynamics, conformational variability, and thermodynamic stability

Proteins are not rigid structures: Protein dynamics, conformational variability, and thermodynamic stability Proteins are not rigid structures: Protein dynamics, conformational variability, and thermodynamic stability Dr. Andrew Lee UNC School of Pharmacy (Div. Chemical Biology and Medicinal Chemistry) UNC Med

More information

Biology Chemistry & Physics of Biomolecules. Examination #1. Proteins Module. September 29, Answer Key

Biology Chemistry & Physics of Biomolecules. Examination #1. Proteins Module. September 29, Answer Key Biology 5357 Chemistry & Physics of Biomolecules Examination #1 Proteins Module September 29, 2017 Answer Key Question 1 (A) (5 points) Structure (b) is more common, as it contains the shorter connection

More information

Paul Sigler et al, 1998.

Paul Sigler et al, 1998. Biological systems are necessarily metastable. They are created, modulated, and destroyed according to a temporal plan that meets the survival needs of the cell, organism, and species...clearly, no biological

More information

BCH 4053 Spring 2003 Chapter 6 Lecture Notes

BCH 4053 Spring 2003 Chapter 6 Lecture Notes BCH 4053 Spring 2003 Chapter 6 Lecture Notes 1 CHAPTER 6 Proteins: Secondary, Tertiary, and Quaternary Structure 2 Levels of Protein Structure Primary (sequence) Secondary (ordered structure along peptide

More information

Enzyme function: the transition state. Enzymes & Kinetics V: Mechanisms. Catalytic Reactions. Margaret A. Daugherty A B. Lecture 16: Fall 2003

Enzyme function: the transition state. Enzymes & Kinetics V: Mechanisms. Catalytic Reactions. Margaret A. Daugherty A B. Lecture 16: Fall 2003 Lecture 16: Enzymes & Kinetics V: Mechanisms Margaret A. Daugherty Fall 2003 Enzyme function: the transition state Catalytic Reactions A B Catalysts (e.g. enzymes) act by lowering the transition state

More information

Catalytic Reactions. Intermediate State in Catalysis. Lecture 16: Catalyzed reaction. Uncatalyzed reaction. Enzymes & Kinetics V: Mechanisms

Catalytic Reactions. Intermediate State in Catalysis. Lecture 16: Catalyzed reaction. Uncatalyzed reaction. Enzymes & Kinetics V: Mechanisms Enzyme function: the transition state Catalytic Reactions Lecture 16: Enzymes & Kinetics V: Mechanisms Margaret A. Daugherty Fall 2003 A B Catalysts (e.g. enzymes) act by lowering the transition state

More information

Biomolecules: lecture 10

Biomolecules: lecture 10 Biomolecules: lecture 10 - understanding in detail how protein 3D structures form - realize that protein molecules are not static wire models but instead dynamic, where in principle every atom moves (yet

More information

Short Announcements. 1 st Quiz today: 15 minutes. Homework 3: Due next Wednesday.

Short Announcements. 1 st Quiz today: 15 minutes. Homework 3: Due next Wednesday. Short Announcements 1 st Quiz today: 15 minutes Homework 3: Due next Wednesday. Next Lecture, on Visualizing Molecular Dynamics (VMD) by Klaus Schulten Today s Lecture: Protein Folding, Misfolding, Aggregation

More information

BIBC 100. Structural Biochemistry

BIBC 100. Structural Biochemistry BIBC 100 Structural Biochemistry http://classes.biology.ucsd.edu/bibc100.wi14 Papers- Dialogue with Scientists Questions: Why? How? What? So What? Dialogue Structure to explain function Knowledge Food

More information

7.88J Protein Folding Problem Fall 2007

7.88J Protein Folding Problem Fall 2007 MIT OpenCourseWare http://ocw.mit.edu 7.88J Protein Folding Problem Fall 2007 For information about citing these materials or our Terms of Use, visit: http://ocw.mit.edu/terms. Lecture Notes - 3 7.24/7.88J/5.48J

More information

Biochemistry,530:,, Introduc5on,to,Structural,Biology, Autumn,Quarter,2015,

Biochemistry,530:,, Introduc5on,to,Structural,Biology, Autumn,Quarter,2015, Biochemistry,530:,, Introduc5on,to,Structural,Biology, Autumn,Quarter,2015, Course,Informa5on, BIOC%530% GraduateAlevel,discussion,of,the,structure,,func5on,,and,chemistry,of,proteins,and, nucleic,acids,,control,of,enzyma5c,reac5ons.,please,see,the,course,syllabus,and,

More information

Dana Alsulaibi. Jaleel G.Sweis. Mamoon Ahram

Dana Alsulaibi. Jaleel G.Sweis. Mamoon Ahram 15 Dana Alsulaibi Jaleel G.Sweis Mamoon Ahram Revision of last lectures: Proteins have four levels of structures. Primary,secondary, tertiary and quaternary. Primary structure is the order of amino acids

More information

Protein structure and folding

Protein structure and folding Protein structure and folding Levels of protein structure Theory of protein folding: Anfinsen s experiment Levinthal s paradox the folding funnel mode 05.11.2014. Amino acids and protein structure Protein

More information

Lecture 2-3: Review of forces (ctd.) and elementary statistical mechanics. Contributions to protein stability

Lecture 2-3: Review of forces (ctd.) and elementary statistical mechanics. Contributions to protein stability Lecture 2-3: Review of forces (ctd.) and elementary statistical mechanics. Contributions to protein stability Part I. Review of forces Covalent bonds Non-covalent Interactions Van der Waals Interactions

More information

Biochemistry - I SPRING Mondays and Wednesdays 9:30-10:45 AM (MR-1307) Lectures 3-4. Based on Profs. Kevin Gardner & Reza Khayat

Biochemistry - I SPRING Mondays and Wednesdays 9:30-10:45 AM (MR-1307) Lectures 3-4. Based on Profs. Kevin Gardner & Reza Khayat Biochemistry - I Mondays and Wednesdays 9:30-10:45 AM (MR-1307) SPRING 2017 Lectures 3-4 Based on Profs. Kevin Gardner & Reza Khayat 1 Outline Overview of protein structure Peptide bonds Secondary structure

More information

Protein Structure Basics

Protein Structure Basics Protein Structure Basics Presented by Alison Fraser, Christine Lee, Pradhuman Jhala, Corban Rivera Importance of Proteins Muscle structure depends on protein-protein interactions Transport across membranes

More information

ALL LECTURES IN SB Introduction

ALL LECTURES IN SB Introduction 1. Introduction 2. Molecular Architecture I 3. Molecular Architecture II 4. Molecular Simulation I 5. Molecular Simulation II 6. Bioinformatics I 7. Bioinformatics II 8. Prediction I 9. Prediction II ALL

More information

BIOC : Homework 1 Due 10/10

BIOC : Homework 1 Due 10/10 Contact information: Name: Student # BIOC530 2012: Homework 1 Due 10/10 Department Email address The following problems are based on David Baker s lectures of forces and protein folding. When numerical

More information

BCMP 201 Protein biochemistry

BCMP 201 Protein biochemistry BCMP 201 Protein biochemistry BCMP 201 Protein biochemistry with emphasis on the interrelated roles of protein structure, catalytic activity, and macromolecular interactions in biological processes. The

More information

Introduction to Protein Folding

Introduction to Protein Folding Introduction to Protein Folding Chapter 4 Proteins: Three Dimensional Structure and Function Conformation - three dimensional shape Native conformation - each protein folds into a single stable shape (physiological

More information

Free energy, electrostatics, and the hydrophobic effect

Free energy, electrostatics, and the hydrophobic effect Protein Physics 2016 Lecture 3, January 26 Free energy, electrostatics, and the hydrophobic effect Magnus Andersson magnus.andersson@scilifelab.se Theoretical & Computational Biophysics Recap Protein structure

More information

12/6/12. Dr. Sanjeeva Srivastava IIT Bombay. Primary Structure. Secondary Structure. Tertiary Structure. Quaternary Structure.

12/6/12. Dr. Sanjeeva Srivastava IIT Bombay. Primary Structure. Secondary Structure. Tertiary Structure. Quaternary Structure. Dr. anjeeva rivastava Primary tructure econdary tructure Tertiary tructure Quaternary tructure Amino acid residues α Helix Polypeptide chain Assembled subunits 2 1 Amino acid sequence determines 3-D structure

More information

Thermodynamics. Entropy and its Applications. Lecture 11. NC State University

Thermodynamics. Entropy and its Applications. Lecture 11. NC State University Thermodynamics Entropy and its Applications Lecture 11 NC State University System and surroundings Up to this point we have considered the system, but we have not concerned ourselves with the relationship

More information

From Amino Acids to Proteins - in 4 Easy Steps

From Amino Acids to Proteins - in 4 Easy Steps From Amino Acids to Proteins - in 4 Easy Steps Although protein structure appears to be overwhelmingly complex, you can provide your students with a basic understanding of how proteins fold by focusing

More information

Student Questions and Answers October 8, 2002

Student Questions and Answers October 8, 2002 Student Questions and Answers October 8, 2002 Q l. Is the Cα of Proline also chiral? Answer: FK: Yes, there are 4 different residues bound to this C. Only in a strictly planar molecule this would not hold,

More information

Biological Chemistry and Metabolic Pathways

Biological Chemistry and Metabolic Pathways Biological Chemistry and Metabolic Pathways 1. Reaction a. Thermodynamics b. Kinetics 2. Enzyme a. Structure and Function b. Regulation of Activity c. Kinetics d. Inhibition 3. Metabolic Pathways a. REDOX

More information

Lecture 15: Enzymes & Kinetics. Mechanisms ROLE OF THE TRANSITION STATE. H-O-H + Cl - H-O δ- H Cl δ- HO - + H-Cl. Margaret A. Daugherty.

Lecture 15: Enzymes & Kinetics. Mechanisms ROLE OF THE TRANSITION STATE. H-O-H + Cl - H-O δ- H Cl δ- HO - + H-Cl. Margaret A. Daugherty. Lecture 15: Enzymes & Kinetics Mechanisms Margaret A. Daugherty Fall 2004 ROLE OF THE TRANSITION STATE Consider the reaction: H-O-H + Cl - H-O δ- H Cl δ- HO - + H-Cl Reactants Transition state Products

More information

Announcements & Lecture Points

Announcements & Lecture Points Announcements & Lecture Points Homework 3 (Klaus Schulten s Lecture): Due Wednesday. Quiz returned, next homework on Wednesday. Today s Lecture: Protein Folding, Misfolding, Aggregation. Experimental Approach

More information

What binds to Hb in addition to O 2?

What binds to Hb in addition to O 2? Reading: Ch5; 158-169, 162-166, 169-174 Problems: Ch5 (text); 3,7,8,10 Ch5 (study guide-facts); 1,2,3,4,5,8 Ch5 (study guide-apply); 2,3 Remember Today at 5:30 in CAS-522 is the second chance for the MB

More information

Enzyme Catalysis & Biotechnology

Enzyme Catalysis & Biotechnology L28-1 Enzyme Catalysis & Biotechnology Bovine Pancreatic RNase A Biochemistry, Life, and all that L28-2 A brief word about biochemistry traditionally, chemical engineers used organic and inorganic chemistry

More information

Solutions and Non-Covalent Binding Forces

Solutions and Non-Covalent Binding Forces Chapter 3 Solutions and Non-Covalent Binding Forces 3.1 Solvent and solution properties Molecules stick together using the following forces: dipole-dipole, dipole-induced dipole, hydrogen bond, van der

More information

MCB100A/Chem130 MidTerm Exam 2 April 4, 2013

MCB100A/Chem130 MidTerm Exam 2 April 4, 2013 MCBA/Chem Miderm Exam 2 April 4, 2 Name Student ID rue/false (2 points each).. he Boltzmann constant, k b sets the energy scale for observing energy microstates 2. Atoms with favorable electronic configurations

More information

Outline. The ensemble folding kinetics of protein G from an all-atom Monte Carlo simulation. Unfolded Folded. What is protein folding?

Outline. The ensemble folding kinetics of protein G from an all-atom Monte Carlo simulation. Unfolded Folded. What is protein folding? The ensemble folding kinetics of protein G from an all-atom Monte Carlo simulation By Jun Shimada and Eugine Shaknovich Bill Hawse Dr. Bahar Elisa Sandvik and Mehrdad Safavian Outline Background on protein

More information

Section Week 3. Junaid Malek, M.D.

Section Week 3. Junaid Malek, M.D. Section Week 3 Junaid Malek, M.D. Biological Polymers DA 4 monomers (building blocks), limited structure (double-helix) RA 4 monomers, greater flexibility, multiple structures Proteins 20 Amino Acids,

More information

PROTEIN STRUCTURE AMINO ACIDS H R. Zwitterion (dipolar ion) CO 2 H. PEPTIDES Formal reactions showing formation of peptide bond by dehydration:

PROTEIN STRUCTURE AMINO ACIDS H R. Zwitterion (dipolar ion) CO 2 H. PEPTIDES Formal reactions showing formation of peptide bond by dehydration: PTEI STUTUE ydrolysis of proteins with aqueous acid or base yields a mixture of free amino acids. Each type of protein yields a characteristic mixture of the ~ 20 amino acids. AMI AIDS Zwitterion (dipolar

More information

Biophysics II. Hydrophobic Bio-molecules. Key points to be covered. Molecular Interactions in Bio-molecular Structures - van der Waals Interaction

Biophysics II. Hydrophobic Bio-molecules. Key points to be covered. Molecular Interactions in Bio-molecular Structures - van der Waals Interaction Biophysics II Key points to be covered By A/Prof. Xiang Yang Liu Biophysics & Micro/nanostructures Lab Department of Physics, NUS 1. van der Waals Interaction 2. Hydrogen bond 3. Hydrophilic vs hydrophobic

More information

Central Dogma. modifications genome transcriptome proteome

Central Dogma. modifications genome transcriptome proteome entral Dogma DA ma protein post-translational modifications genome transcriptome proteome 83 ierarchy of Protein Structure 20 Amino Acids There are 20 n possible sequences for a protein of n residues!

More information

Papers listed: Cell2. This weeks papers. Chapt 4. Protein structure and function. The importance of proteins

Papers listed: Cell2. This weeks papers. Chapt 4. Protein structure and function. The importance of proteins 1 Papers listed: Cell2 During the semester I will speak of information from several papers. For many of them you will not be required to read these papers, however, you can do so for the fun of it (and

More information

Outline. Levels of Protein Structure. Primary (1 ) Structure. Lecture 6:Protein Architecture II: Secondary Structure or From peptides to proteins

Outline. Levels of Protein Structure. Primary (1 ) Structure. Lecture 6:Protein Architecture II: Secondary Structure or From peptides to proteins Lecture 6:Protein Architecture II: Secondary Structure or From peptides to proteins Margaret Daugherty Fall 2003 Outline Four levels of structure are used to describe proteins; Alpha helices and beta sheets

More information

Protein Dynamics. The space-filling structures of myoglobin and hemoglobin show that there are no pathways for O 2 to reach the heme iron.

Protein Dynamics. The space-filling structures of myoglobin and hemoglobin show that there are no pathways for O 2 to reach the heme iron. Protein Dynamics The space-filling structures of myoglobin and hemoglobin show that there are no pathways for O 2 to reach the heme iron. Below is myoglobin hydrated with 350 water molecules. Only a small

More information

Lecture 34 Protein Unfolding Thermodynamics

Lecture 34 Protein Unfolding Thermodynamics Physical Principles in Biology Biology 3550 Fall 2018 Lecture 34 Protein Unfolding Thermodynamics Wednesday, 21 November c David P. Goldenberg University of Utah goldenberg@biology.utah.edu Clicker Question

More information

Biochemistry Prof. S. DasGupta Department of Chemistry Indian Institute of Technology Kharagpur. Lecture - 06 Protein Structure IV

Biochemistry Prof. S. DasGupta Department of Chemistry Indian Institute of Technology Kharagpur. Lecture - 06 Protein Structure IV Biochemistry Prof. S. DasGupta Department of Chemistry Indian Institute of Technology Kharagpur Lecture - 06 Protein Structure IV We complete our discussion on Protein Structures today. And just to recap

More information

arxiv:cond-mat/ v1 7 Jul 2000

arxiv:cond-mat/ v1 7 Jul 2000 A protein model exhibiting three folding transitions Audun Bakk Department of Physics, Norwegian University of Science and Technology, NTNU, N-7491 Trondheim, Norway arxiv:cond-mat/0007130v1 7 Jul 2000

More information

Protein structure forces, and folding

Protein structure forces, and folding Harvard-MIT Division of Health Sciences and Technology HST.508: Quantitative Genomics, Fall 2005 Instructors: Leonid Mirny, Robert Berwick, Alvin Kho, Isaac Kohane Protein structure forces, and folding

More information

Biomolecules: lecture 9

Biomolecules: lecture 9 Biomolecules: lecture 9 - understanding further why amino acids are the building block for proteins - understanding the chemical properties amino acids bring to proteins - realizing that many proteins

More information

Outline. Levels of Protein Structure. Primary (1 ) Structure. Lecture 6:Protein Architecture II: Secondary Structure or From peptides to proteins

Outline. Levels of Protein Structure. Primary (1 ) Structure. Lecture 6:Protein Architecture II: Secondary Structure or From peptides to proteins Lecture 6:Protein Architecture II: Secondary Structure or From peptides to proteins Margaret Daugherty Fall 2004 Outline Four levels of structure are used to describe proteins; Alpha helices and beta sheets

More information

Analyze the roles of enzymes in biochemical reactions

Analyze the roles of enzymes in biochemical reactions ENZYMES and METABOLISM Elements: Cell Biology (Enzymes) Estimated Time: 6 7 hours By the end of this course, students will have an understanding of the role of enzymes in biochemical reactions. Vocabulary

More information

NMR Characterization of Partially Folded and Unfolded Conformational Ensembles of Proteins

NMR Characterization of Partially Folded and Unfolded Conformational Ensembles of Proteins Elisar Barbar Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701 NMR Characterization of Partially Folded and Unfolded Conformational Ensembles of Proteins Abstract: Studies of

More information

Charged amino acids (side-chains)

Charged amino acids (side-chains) Proteins are composed of monomers called amino acids There are 20 different amino acids Amine Group Central ydrocarbon N C C R Group Carboxyl Group ALL amino acids have the exact same structure except

More information

Presenter: She Zhang

Presenter: She Zhang Presenter: She Zhang Introduction Dr. David Baker Introduction Why design proteins de novo? It is not clear how non-covalent interactions favor one specific native structure over many other non-native

More information

Archives of Biochemistry and Biophysics

Archives of Biochemistry and Biophysics Archives of Biochemistry and Biophysics 531 (2013) 24 33 Contents lists available at SciVerse ScienceDirect Archives of Biochemistry and Biophysics journal homepage: www.elsevier.com/locate/yabbi Review

More information

schematic diagram; EGF binding, dimerization, phosphorylation, Grb2 binding, etc.

schematic diagram; EGF binding, dimerization, phosphorylation, Grb2 binding, etc. Lecture 1: Noncovalent Biomolecular Interactions Bioengineering and Modeling of biological processes -e.g. tissue engineering, cancer, autoimmune disease Example: RTK signaling, e.g. EGFR Growth responses

More information

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

Dihedral Angles. Homayoun Valafar. Department of Computer Science and Engineering, USC 02/03/10 CSCE 769 Dihedral Angles Homayoun Valafar Department of Computer Science and Engineering, USC The precise definition of a dihedral or torsion angle can be found in spatial geometry Angle between to planes Dihedral

More information

Chem. 27 Section 1 Conformational Analysis Week of Feb. 6, TF: Walter E. Kowtoniuk Mallinckrodt 303 Liu Laboratory

Chem. 27 Section 1 Conformational Analysis Week of Feb. 6, TF: Walter E. Kowtoniuk Mallinckrodt 303 Liu Laboratory Chem. 27 Section 1 Conformational Analysis TF: Walter E. Kowtoniuk wekowton@fas.harvard.edu Mallinckrodt 303 Liu Laboratory ffice hours are: Monday and Wednesday 3:00-4:00pm in Mallinckrodt 303 Course

More information

NH 2. Biochemistry I, Fall Term Sept 9, Lecture 5: Amino Acids & Peptides Assigned reading in Campbell: Chapter

NH 2. Biochemistry I, Fall Term Sept 9, Lecture 5: Amino Acids & Peptides Assigned reading in Campbell: Chapter Biochemistry I, Fall Term Sept 9, 2005 Lecture 5: Amino Acids & Peptides Assigned reading in Campbell: Chapter 3.1-3.4. Key Terms: ptical Activity, Chirality Peptide bond Condensation reaction ydrolysis

More information

arxiv: v1 [cond-mat.soft] 22 Oct 2007

arxiv: v1 [cond-mat.soft] 22 Oct 2007 Conformational Transitions of Heteropolymers arxiv:0710.4095v1 [cond-mat.soft] 22 Oct 2007 Michael Bachmann and Wolfhard Janke Institut für Theoretische Physik, Universität Leipzig, Augustusplatz 10/11,

More information

Proteins polymer molecules, folded in complex structures. Konstantin Popov Department of Biochemistry and Biophysics

Proteins polymer molecules, folded in complex structures. Konstantin Popov Department of Biochemistry and Biophysics Proteins polymer molecules, folded in complex structures Konstantin Popov Department of Biochemistry and Biophysics Outline General aspects of polymer theory Size and persistent length of ideal linear

More information

Essential Forces in Protein Folding

Essential Forces in Protein Folding Essential Forces in Protein Folding Dr. Mohammad Alsenaidy Department of Pharmaceutics College of Pharmacy King Saud University Office: AA 101 msenaidy@ksu.edu.sa Previously on PHT 426!! Amino Acid sequence

More information

Protein Structure Bioinformatics Introduction

Protein Structure Bioinformatics Introduction 1 Swiss Institute of Bioinformatics Protein Structure Bioinformatics Introduction Basel, 27. September 2004 Torsten Schwede Biozentrum - Universität Basel Swiss Institute of Bioinformatics Klingelbergstr

More information

Introduction to" Protein Structure

Introduction to Protein Structure Introduction to" Protein Structure Function, evolution & experimental methods Thomas Blicher, Center for Biological Sequence Analysis Learning Objectives Outline the basic levels of protein structure.

More information

Biological Thermodynamics

Biological Thermodynamics Biological Thermodynamics Classical thermodynamics is the only physical theory of universal content concerning which I am convinced that, within the framework of applicability of its basic contents, will

More information

Lecture 27. Transition States and Enzyme Catalysis

Lecture 27. Transition States and Enzyme Catalysis Lecture 27 Transition States and Enzyme Catalysis Reading for Today: Chapter 15 sections B and C Chapter 16 next two lectures 4/8/16 1 Pop Question 9 Binding data for your thesis protein (YTP), binding

More information

Introduction to Computational Structural Biology

Introduction to Computational Structural Biology Introduction to Computational Structural Biology Part I 1. Introduction The disciplinary character of Computational Structural Biology The mathematical background required and the topics covered Bibliography

More information

A. Reaction Mechanisms and Catalysis (1) proximity effect (2) acid-base catalysts (3) electrostatic (4) functional groups (5) structural flexibility

A. Reaction Mechanisms and Catalysis (1) proximity effect (2) acid-base catalysts (3) electrostatic (4) functional groups (5) structural flexibility (P&S Ch 5; Fer Ch 2, 9; Palm Ch 10,11; Zub Ch 9) A. Reaction Mechanisms and Catalysis (1) proximity effect (2) acid-base catalysts (3) electrostatic (4) functional groups (5) structural flexibility B.

More information

High Specificity and Reversibility

High Specificity and Reversibility Lecture #8 The Cell as a Machine High Specificity and Reversibility In considering the problem of transcription factor binding in the nucleus and the great specificity that is called for to transcribe

More information

Protein Folding In Vitro*

Protein Folding In Vitro* Protein Folding In Vitro* Biochemistry 412 February 29, 2008 [*Note: includes computational (in silico) studies] Fersht & Daggett (2002) Cell 108, 573. Some folding-related facts about proteins: Many small,

More information

7.12. PROTEIN FOLDING AND MISFOLDING 43

7.12. PROTEIN FOLDING AND MISFOLDING 43 7.12. PROTEIN FOLDING AND MISFOLDING 43 http://www.life.illinois.edu/biophysics/401/ Protein folding usually refers to the process that results in acquisition of the native structure from a completely

More information

An Introduction to Metabolism. Chapter 8

An Introduction to Metabolism. Chapter 8 An Introduction to Metabolism Chapter 8 METABOLISM I. Introduction All of an organism s chemical reactions Thousands of reactions in a cell Example: digest starch use sugar for energy and to build new

More information

Fluorine in Peptide and Protein Engineering

Fluorine in Peptide and Protein Engineering Fluorine in Peptide and Protein Engineering Rita Fernandes Porto, February 11 th 2016 Supervisor: Prof. Dr. Beate Koksch 1 Fluorine a unique element for molecule design The most abundant halogen in earth

More information

It s the amino acids!

It s the amino acids! Catalytic Mechanisms HOW do enzymes do their job? Reducing activation energy sure, but HOW does an enzyme catalysis reduce the energy barrier ΔG? Remember: The rate of a chemical reaction of substrate

More information

MBLG lecture 5. The EGG! Visualising Molecules. Dr. Dale Hancock Lab 715

MBLG lecture 5. The EGG! Visualising Molecules. Dr. Dale Hancock Lab 715 MBLG lecture 5 Dr. Dale Hancock D.Hancock@mmb.usyd.edu.au Lab 715 The EGG! Visualising Molecules In molecular biology and biochemistry it is better to view molecules as killer pythons rather than smarties.

More information

Why Is Molecular Interaction Important in Our Life

Why Is Molecular Interaction Important in Our Life Why Is Molecular Interaction Important in ur Life QuLiS and Graduate School of Science iroshima University http://www.nabit.hiroshima-u.ac.jp/iwatasue/indexe.htm Suehiro Iwata Sept. 29, 2007 Department

More information

MCB100A/Chem130 MidTerm Exam 2 April 4, 2013

MCB100A/Chem130 MidTerm Exam 2 April 4, 2013 MCB1A/Chem13 MidTerm Exam 2 April 4, 213 Name Student ID True/False (2 points each). 1. The Boltzmann constant, k b T sets the energy scale for observing energy microstates 2. Atoms with favorable electronic

More information

4. The Michaelis-Menten combined rate constant Km, is defined for the following kinetic mechanism as k 1 k 2 E + S ES E + P k -1

4. The Michaelis-Menten combined rate constant Km, is defined for the following kinetic mechanism as k 1 k 2 E + S ES E + P k -1 Fall 2000 CH 595C Exam 1 Answer Key Multiple Choice 1. One of the reasons that enzymes are such efficient catalysts is that a) the energy level of the enzyme-transition state complex is much higher than

More information

2054, Chap. 8, page 1

2054, Chap. 8, page 1 2054, Chap. 8, page 1 I. Metabolism: Energetics, Enzymes, and Regulation (Chapter 8) A. Energetics and work 1. overview a. energy = ability to do work (1) chemical, transport, mechanical (2) ultimate source

More information

Chapter 6- An Introduction to Metabolism*

Chapter 6- An Introduction to Metabolism* Chapter 6- An Introduction to Metabolism* *Lecture notes are to be used as a study guide only and do not represent the comprehensive information you will need to know for the exams. The Energy of Life

More information

INVESTIGATING NONNATIVE CONTACTS IN PROTEIN FOLDING. A Thesis. Presented to. The Graduate Faculty of The University of Akron. In Partial Fulfillment

INVESTIGATING NONNATIVE CONTACTS IN PROTEIN FOLDING. A Thesis. Presented to. The Graduate Faculty of The University of Akron. In Partial Fulfillment INVESTIGATING NONNATIVE CONTACTS IN PROTEIN FOLDING A Thesis Presented to The Graduate Faculty of The University of Akron In Partial Fulfillment of the Requirements for the Degree Master of Science Chong

More information

Problems from Previous Class

Problems from Previous Class 1 Problems from Previous lass 1. What is K m? What are the units of K m? 2. What is V max? What are the units of V max? 3. Write down the Michaelis-Menten equation. 4. What order of reaction is the reaction

More information

An Introduction to Metabolism

An Introduction to Metabolism An Introduction to Metabolism I. All of an organism=s chemical reactions taken together is called metabolism. A. Metabolic pathways begin with a specific molecule, which is then altered in a series of

More information

STRUCTURAL BIOINFORMATICS. Barry Grant University of Michigan

STRUCTURAL BIOINFORMATICS. Barry Grant University of Michigan STRUCTURAL BIOINFORMATICS Barry Grant University of Michigan www.thegrantlab.org bjgrant@umich.edu Bergen, Norway 28-Sep-2015 Objective: Provide an introduction to the practice of structural bioinformatics,

More information

Biophysik der Moleküle. 4. Vorlesung Rädler WS Protein folding. - Afinsen hypothesis - hydrophobic interaction. 28. Oct.

Biophysik der Moleküle. 4. Vorlesung Rädler WS Protein folding. - Afinsen hypothesis - hydrophobic interaction. 28. Oct. Biophysik der Moleküle 4. Vorlesung Rädler WS 2010 Protein folding - Afinsen hypothesis - hydrophobic interaction 28. Oct. 2010 Protein Unfolding: Sushi Restaurant 1. Distinguish salmon roe from imitation

More information