Download Proteins = polymers of 20 amino acids, connected by peptide bonds

9/6/11
Planned schedule for Biomolecular Structure 2011
Updates including additional reading and assignments will be posted on course website:
http://people.chem.umass.edu/thompson/Courses/BioStruct/Fall2011
Syllabus (last updated 9/5/11)
CHEM 627 Fall 2011
BIOMOLECULAR STRUCTURE
TTh 9:30-10:45, LGRT 1234
Schedule
This course is aimed at first and second year graduate students and
advanced undergraduates interested in understanding the structures and
mechanisms of macromolecular structures in biology. You will learn about
the physical basis for these structures, their folding, stability, and
interactions with other molecules, as well as the structural basis of
catalytic mechanisms. You will gain a working knowledge of computer
programs for manipulating and understanding macromolecular structures
and be introduced to X-ray crystallography and NMR techniques used for
structure determination. This is an important foundation for students
whose research focuses on understanding proteins and nucleic acids, or
synthesizing molecules to mimic or interact with them.
INSTRUCTOR: Lynmarie Thompson, LGRT 403E, 545-0827, office hours by appointment
REQUIRED TEXT: Protein Structure & Function, by Gregory Petsko & Dagmar Ringe.
PREREQUISITE: One year of organic chemistry. Introductory biochemistry or permission of
instructor.
GRADING:
25%
25%
25%
25%
Exam I
Due 9:30 am Oct 13
Exam II
Due 9:30 am Nov 22
Presentation
Nov 22 - Dec 8
Homework/quizzes 9:30 am on due date/Unannounced
Grading cutoffs (minimal): A = 90-100, B = 80-89, C = 70-79, D = 60-69, F = below 60
Grading may also be curved upward later (eg a score of 89 may earn an A).
Images: Molecular machines involved in harnessing energy (top, proteins bound to
membrane) and self-replication (proteins bound to DNA, right side). Adapted from Protein
Data Bank poster (pdf 5MB).
Date
Tu 9/6
Th 9/8
Tu 9/13
Th 9/15
Tu 9/20
Th 9/22
Tu
Th
Tu
Th
Tu
Th
Tu
Th
Tu
Th
Tu
Th
Tu
Th
Tu
Th
Tu
Th
Tu
Th
Tu
Th
9/27
9/29
10/4
10/6
10/11
10/13
10/18
10/20
10/25
10/27
11/1
11/3
11/8
11/10
11/15
11/17
11/22
11/24
11/29
12/1
12/6
12/8
Topic
Amino acids & Primary structure
Secondary structure
Pymol Workshop I in ISB 325 (CRC)
Tertiary structure
Protein folding & stability
Universe of structures; Quaternary
structure
Protein binding and flexibility
X-ray crystallography
Pymol Workshop II in ISB 325 (CRC)
X-ray crystallography
NO CLASS (UMass Monday)
NMR
Catalysis
Nucleic acid structure
Nucleic acid structure
Membrane protein structures
Controlling proteins
Controlling proteins
The “omic” era
Deducing structure from sequence
Pymol Workshop III: movie making
Deducing function
Student Presentations
NO CLASS
Student Presentations
Student Presentations
Student Presentations
Student Presentations
Reading*
1-0 to 1-4
1-5 to 1-8
1-9 to 1-11
1-12 to 1-14
1-15 to 1-21
Homework 1 due
1-22, 2-0 to 2-5
5-1 to 5-3
Exam 1 distributed
Exam 1 due
2-6 to 2-16
3-0 to 3-10
3-11 to 3-20
4-0, 4-4; Exam 2 distributed
4-6&7, 4-14&15
Exam 2 due
Rest of chapter 4
Happy Thanksgiving!
Quiz
*A number of papers from the primary literature will also be assigned. Readings are in
Protein Structure & Function by Petsko & Ringe, unless otherwise noted.
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Proteins
= polymers of 20 amino acids, connected by peptide bonds
Covalent bonds determine only primary structure = defined sequence of amino acids
Protein functions -- what is the structural basis?
Binding
Catalysis
Switching
Structural
What protein are you interested in?
Genes and disease
Branden & Tooze, Intro to Protein Structure
Secondary, tertiary & quaternary structure due to noncovalent interactions (+ S-S)  unique 3-dimensional structure
Proteopedia
Protein Data Bank
Pymol
1
9/6/11
Amino acid sidechains
pKa s
Environment shifts
How do proteins fold into unique 3D structures?
≈5
12.5
6.0
How do proteins carry out such a huge array of functions?
8.3
10.8
≈9
Predominant forms at pH 7.
2
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RNA world hypothesis
Why use proteins to carry out chemistry of life?
X-Pro
Torsion angles:
Chi angles specify sidechain conformation.
Focus on phi & psi which specify backbone conformation.
Berg: Biochemistry
3
9/6/11
Peptide backbone conformation
torsion or dihedral angles: -180˚ → +180˚
Fixed:
CO-N = peptide bond (ω) = planar
typically =180˚ (trans)
deviations ∆ω = -20 to +10 OK
some X-Pro = 0˚ (cis)
Variable:
N-Cα torsion = phi (ϑ)
Cα-CO torsion = psi (ψ)
Beta turn
Reverse turn
Hairpin turn
β:-130,+125
α:-60,-50
Berg: Biochemistry
4
9/6/11
Alpha Helix
3.6 residues/turn; COi to NHi+4 H bonds
1.5Å/residue -- compact
Helical wheels, sidechains out
Helical wheels:
3.6 residues per turn
Repeats after 5 turns = 18 residues
(blue offset to see repeat)
5