BIO466 /NS 566 Biophysics: Molecules and Systems Spring 2011 | Faculty of Engineering and Natural Sciences

BIO466 /NS 566 Biophysics: Molecules and Systems Spring2011
(February 7, 2011)
Instructor: Deniz Sezer
Office: FENS G021 Lectures: Wed 12:40-13:30 FENS L067
E-mail: dsezer@sabanciuniv.edu Thr 11:40-13:30 FENS L067
Office Phone: 483-9881
Web: http://myweb.sabanciuniv.edu/dsezer

Course Description: The course is organized around one main question: How do “intelligent”
molecular-level biological processes emerge from nonintelligent driving forces? To pose the question in its proper setting, we first get familiar with the world in which biological molecules live, where everything—from stability of structures to operation principles of devices—looks very different than its counterpart in our everyday world. We then resort to the concepts of statistical and thermal physics, which provide us with a quantitative toolbox for making sense of the changes caused by driving forces at the molecular level. With knowledge about biomolecular structure and understanding of entropy and free energy in place, we turn to the treatment of basic molecular processes like binding of small molecules (e.g., a hormone) by big molecules (e.g., a receptor) and catalysis of biological reactions by enzymes. The dynamic nature of the cellular skeleton and the workings of energy-transducing molecular motors (think about our muscles) is considered next. At the end, we examine how electrical signals are generated and travel along excitable cells like the neurons in our brain. The description of electrical signals at the level of a cell is followed by a presentation of the underlying conduction and gating processes at the level of a single protein molecule responsible for the selective and controlled
passage of ions.

Who can take this course: The course is catered to advanced undergraduate and starting graduate students in the biological sciences, engineering, and physical science. Since the focus is on molecules and molecular assemblies working in the context of a living cell, the engineering and physical science students are expected to be interested in questions related to the molecular aspects of biology. The workings of these biological molecules, however, are conceptualized using the mathematical language of thermal and statistical physics. Thus, the biology students are expected to be willing to use calculus and work with quantitative models. In some sense, this course is the advanced version of the first-year Science of Nature courses (NS 101 and NS 102) offered at Sabancı, in which students are expected to realize that the boundaries between physics, chemistry, and biology are largely artificial and counterproductive for the understanding of natural phenomena.

Evaluation:
Homework and quizzes 15 %
Exam I (Mar 23) 25 %
Exam II (May 12) 25 %
Comprehensive final exam 35 %

Course Content:
I. The nanoworld of biological molecules
A. Cells, molecules and numbers
1. Sizing up E. Coli and yeast
2. Hemoglobin by the numbers
3. Bacterial viruses and bacteria
B. Structure of biological molecules
1. Structural chemistry
2. -helices, -sheets and protein structure
3. DNA and the double helix
4. Lipids and lipid bilayers
5. Integrated molecular devices
C. Thermal energy rules the nanoworld
1. Forces and friction
2. Diffusion and viscosity
3. Chemoreception and flow through a channel
4. Diffusion under force and the Smoluchowski equation
II. Molecular driving forces
A. Thermodynamics
1. Energy, entropy and free energy
2. Thermal and chemical equilibrium
3. Thermodynamic machines
B. Statistical mechanics
1. Lattice models of ligand binding and DNA recognition
2. Random walks and macromolecular structure
3. Microscopic view of diffusion
4. Chemical kinetics and the chemical potential
5. Electrostatics for salty solutions
C. Applications
1. Protein charge and electrophoresis
2. Self-assembly of lipids, protein folding and differential scanning calorimetry
III. Binding, conformational exchange, and catalysis
A. Ligand binding and conformational transitions
1. Thermodynamics of binding: Isothermal titration calorimetry
2. Kinetics of binding
3. Conformational exchange
B. Enzymes
1. Enzyme turnover, diffusion, and Michaelis-Menten kinetics
2. Catalytic strategies and stabilization of the transition state
C. Applications
1. Allostery and cooperative binding in Hemoglobin
2. Binding of covalently bound signaling domains
3. Fluctuating enzymes: Coupling of conformational exchange and catalysis
IV. Cellular shape and intracellular transport
A. The cytoskeleton
1. Beam theory and cytoskeletal structure
2. Dynamics of cytoskeletal polymerization
B. Molecular motors
1. Brownian ratchet
2. Motor stepping from a free-energy perspective
V. Biological electricity and ion conduction
A. Microscopic picture: The action potential
1. Nernst equation and the membrane potential
2. Nerve impulses and the Hodgkin-Huxley model
B. Nanoscopic picture: Single-channel conduction and gating
1. Ion conduction of a potassium channel
2. Gating of a potassium channel

Textbooks:
PBoC Phillips, Kondev and Theriot, Physical Biology of the Cell, Garland Science, 2009.
BP Nelson, Biological Physics: Energy, Information, Life, updated 1st edition, W.H. Freeman and Co., 2008.

Reference Books:
MDF Dill and Bromberg, Molecular Driving Forces: Statistical Thermodynamics in Chemistry and Biology, 1st edition, Garland Science, 2004.
MBoC Alberts, Johnson, Lewis, Raff, Roberts, and Walter, Molecular Biology of the Cell, 5th edition, Garland Science, 2008.
Bioch Berg, Tymoczko and Stryer, Biochemistry, 6th edition, W.H. Freeman, 2006.
BNT Goodsell, Bionanotechnology: Lessons from Nature, Wiley-Liss, Inc., 2004.
WiL Schr¨odinger, What is Life?, Cambridge University Press, 1992.