This course offers a physicist's perspective on the building blocks of the living
world, ... A rigorous treatment of a wide range of biophysical techniques
commonly.
PHY332H5 – Molecular Biophysics Description This course offers a physicist's perspective on the building blocks of the living world, such as nucleic acids, proteins and lipids. The course will cover topics such as symmetry, structural complexity of the biological macromolecules, molecular interactions in the cellular environment and the impact for the biological function. Basic concepts from mechanics and thermodynamics will be applied specifically to proteins and DNA in order to understand structural transitions, stabilizing interactions, reaction dynamics and equilibrium. A rigorous treatment of a wide range of biophysical techniques commonly used in life sciences, such as optical spectroscopy, radiation scattering and singlemolecule methods, will be accompanied by recent examples from the molecular biophysics research. Prerequisite: PHY242H5, JCP221H5/CHM221H5 Recommended Preparation: JCP321H5 Offered in alternate years, alternating with PHY333H5; offered in 2013-14. Instructor: Claudiu Gradinaru, PhD Associate Professor of Physics Department of Chemical and Physical Sciences Room DV4043 905-828-3833
[email protected] Office hours: Friday 2-3 pm or anytime my office door is open Class Schedule: Lectures: Tuesday, 9-11 am, IB 340 Tutorials: Friday, 3-4 pm, IB 377 Learning Objectives: By the end of this course the students are expected to know how to apply Physics principles in order to understand the structure and the dynamics of biological systems, and which experimental approaches are best suited to extract this quantitative information. Course Syllabus: 1. Macromolecules: conformations, configurations and symmetry; the structure of proteins and nucleic acids 2. Molecular Thermodynamics: molecular forces, energy, entropy and the stability of biological structures 3. Statistical Thermodynamics: structural transitions in biopolymers, folding/unfolding of proteins and nucleic acids 4. Biophysical Methods – theory and experiment: • calorimetry • UV/VIS absorption and fluorescence spectroscopy
• • •
linear and circular dichroism radiation scattering single-molecule methods
Textbook: Principles of Physical Biochemistry, van Holde, Johnson & Ho, 2006 Recommended Material: Biophysical Chemistry, Cantor & Schimmel, I-III, 1980 Evaluation Scheme: Quizzes Assignments Oral presentation of a biophysics research topic Final exam
10% 35% 15% 40%
Lateness Penalties: Late penalty on homework assignments and quizzes: zero score once the deadline passed. Medical or other excuses will not be accepted as a reason for missing homework, which typically extends over several days (excepting, of course, in the unfortunate circumstance of a prolonged, serious illness). For the oral presentation, 50% of the mark if the presentation file is submitted within 1(one) working day after the due date, a mark of zero otherwise. Issues associated with illness, pandemic or other absence: 1. Requests for special consideration due to absence can be submitted up to one week after an assignment deadline by 5pm of that day. Extension of this deadline will only be considered if the student is incapacitated past the one-week deadline. Within one week of the date of the missed work, students should submit to the course instructor a signed letter explaining the reason for their absence. The letter should include the student's name, phone number, email address, student number and lab/tutorial section number as well as the date of and the description of the missed work. A doctor's note or other appropriate documentation regarding the absence should be stapled to the letter. If the explanation for the missed work is deemed reasonable after verification of the documentation, the final exam mark will be used as the mark for the missed work. If the explanation is considered unreasonable or no letter is submitted within one week of the missed work, a mark of zero will be assigned for the missed work. 2. Students must request special consideration by means of Email to the course instructor. 3. Supporting documentation required in addition to a ROSI absence declaration must be supplied in person. Absence due to illness requires a UofT medical certificate. All supporting documents will be examined to determine whether special consideration is granted. In a circumstance such as an outbreak that affects many in the class, then alternatives in terms of lecture delivery, due dates and marking scheme will be arranged to support all members of the class.
Important Dates (Fall 2013): Assignments' due dates (roughly): • #1: 27 September • #2: 8 October • #3: 25 October • #4: 5 November • #5: 19 November Oral presentation: 29 November (Friday), 3-5 pm, location TBA Course Outline: Lecture 1 Introduce the instructor: background, studies, research expertise Introduce the course: • What is biophysics? • What will you learn? – a general outline of the course • Outlook: what is the use of what you will have learned here? Course administration: marking scheme, office hours, Blackboard material Lecture 2
Macromolecules: conformations and configurations Molecular interactions and the water environment Symmetry in biomolecules The hierarchy of protein structure: amino acids and peptide bonds; the secondary structure: α-helices, β-sheets, collagen; the tertiary and the quaternary structure.
Lecture 3
The structure of nucleic acids: chemical composition, the helical forms of DNA, RNA folding and DNA supercoiling
Tutorial 1
Use Rasmol software to explore the structure of biological macromolecules
Lecture 4
A brief introduction to thermodynamics: • Heat, work and the first principle • Entropy, equilibrium and the second principle
Tutorial 2
More applications of thermodynamics to biology
Lecture 5
Gibbs free energy Thermochemistry and calorimetry
Tutorial 3
Problems on thermodynamics and calorimetry
Lecture 6
Molecular mechanics, energy potentials and stabilizing interactions in macromolecules
Tutorial 4
Problems on thermodynamics and molecular mechanics
Lecture 7
Molecular thermodynamics: simulating macromolecular structures
Tutorial 5
Problems related to molecular interactions and structure simulations
Lecture 8
Statistical thermodynamics: general concepts, structural transitions in polypeptides
Tutorial 6
How to apply statistical methods to biological problems
Lecture 9
Statistical description of structural transitions in nucleic acids. Review of the topics for midterm test.
Tutorial 7
Statistical thermodynamics problems; preparation for midterm test.
Lecture 10
Scattering of radiation (light, X-ray, neutrons) from solutions of macromolecules.
Tutorial 8
Problems and practical applications related to the scattering theory
Lecture 11
Quantum Mechanics 101: postulates, Schrodinger equation, transition energies, the particle in the box, the hydrogen atom, molecular orbitals
Lecture 12
Absorption Spectroscopy- quantum mechanics at work. Lambert-Beer Law, electronic transitions in macromolecules: energy, intensity, dipoles. Einstein coefficients.
Tutorial 9
UV/VIS spectroscopic analysis of biopolymers: lab tutorial and discussion.
Lecture 13
Linear Dichroism: transition dipole moments and the orientation of biomolecules Circular Dichroism: the molecular origins of the rotational strength of molecules
Tutorial 10 Applications of polarized light interactions with chromophores in proteins and DNA - case studies from literature. Lecture 14
Fluorescence Spectroscopy I: basic principles, observables and instrumentation Fluorescence Spectroscopy II: the fluorescence of proteins and DNA, fluorescence resonance energy transfer (FRET)
Tutorial 11 Fluorescence applications and problems Review of the topics for the final exam.
