Biomolecular Processes as Concurrent Computation

An interdisciplinary course at Feinberg Graduate School of the Weizmann Institute of Science, Israel

News, Plan, Exercises, Administrative Stuff, Useful Stuff

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Lecture hours	Thursday 11:00-13:00 (Wolfson lecture hall) First meeting – 19 April 2001
Lecturers	Prof. Ehud Shapiro Aviv Regev
Teaching Assistant	Barak Shenhav
Questions, comments, etc.	Barak Shenhav, barak.shenhav@weizmann.ac.il, Tel. 3098
Credits	2

News

15-Apr-2001 Please register as soon as possible.

3-June-2001 Please, note requirements.

Plan:

Week		Topic	Exercise
1	19 April 2001	Introduction	The reaction K + F => K^+ + F^-
2	26 April 2001	No class	No exercise
3	3 May 2001	The electron theory of chemical bonds	Chemical bonds
4	10 May 2001	Molecules, Radicals and Functional Groups	Modular representation of reactions
5	17 May 2001	Polymers	Proteins
6	24 May 2001	Tracing and debugging	Quantities
7	31 May 2001	Enzymatic reactions	Enzymes
8	7 June 2001	Molecular machines	No exercise
9	14 June 2001	Regulatory networks	Regulatory Circuits
10	21 June 2001	Project guidelines and Molecular computing	No exercise
11	28 June 2001	No class	No exercise
12	5 July 2001	Signal transduction	No exercise

Class 1: Introduction

· Short (class) version of slides (PowerPoint, HTML)

· Long version of the slides, combining class 1 and 2 with minor corrections (PowerPoint, HTML)

· Biospi appendices (postscript)

· The NaCl example.

Class 2: The electron theory of chemical bonds

· Slides (PowerPoint, HTML)

· Examples:

- K + Na + 2Cl (knacl_2.cp)

- Mg + Cl (mgcl2_3.cp) – Explicit intermediate state

- Mg + Cl (mgcl2_4.cp) – Implicit intermediate state

- H + Cl (hcl_5.cp) – Local channel declaration

- H + Cl (hcl_6.cp) – Local channel declaration, alternative

- H + H (h2_7.cp) – Symmetric interaction

- O + O (o2_8.cp) – Symmetric interaction, two electrons, naive approach

- O + O (o2_9.cp) – More complex approach

- H2O (h2o_10.cp) – External calls

Class 3: Molecules, Radicals and Functional Groups

· Slides, slightly corrected (PowerPoint, HTML)

· Examples:

- C + O + H (coh_4.cp) – Original version

- C + O + H (coh_new.cp) – A slightly corrected version

- Condensation and hydrolysis (condensation_peptide_1.cp)

- Other

Class 4: Polymers

· Slides, as presented in class (PowerPoint, HTML)

· Long version of the slides, combining class 4 and 5 (PowerPoint, HTML)

· Examples:

- Polyethylene (polyethylene_1.cp)

- Nucleotides (phosphodiester_sugar_phosphate_7a.cp)

- More

Class 5: Tracing and debugging

· Slides, as presented in class (PowerPoint, HTML)

· Examples:

- Time (status.cp) – retrieve simulated system time

- More

Class 6: Enzymatic reactions

· Slides, as presented in class (PowerPoint, HTML)

· Examples

Class 7: Molecular machines

· Slides (PowerPoint, HTML)

· Examples:

- RNA (rnapol_1.cp) – RNA polymerization

- Glycogen (glycogen_1.cp) – Glycogen polymerization

Class 8: Regulatory networks

· Slides, as presented in class (PowerPoint, HTML)

· Examples

Class X: Molecular computing

· Slides, as presented in class (PowerPoint, HTML)

· Examples:

- Strings (eg.cp) – String manipulation

- Automaton (automaton.cp) – Cellular automaton

Class 9: Signal transduction

· Slides, as presented in class (PowerPoint, HTML)

Exercises:

Exercise 1: The reaction K + F => K⁺ + F^- (due by May 6^rd)

Attached code (kf_spawn.cp):

% This piece of code serves to spawn off N1 "K processes" and N2 "F processes".

% Incorporate it into your program as one of the processes

System(N1,N2)::= << CREATE_K(N1) | CREATE_F(N2) .

CREATE_K(C)::= {C =< 0} , true ;

{C > 0} , {C--} | K | self .

CREATE_F(C)::= {C =< 0} , true ;

{C > 0} , {C--} | F | self

>> .

You should use the script spi2t in order to convert the record file to a .table and .names files.

Sample of outputs:

Question 1	Question 2a	Question 2b	Question 3a	Question 3b	Question 4a	Question 4b

Exercise 2: Chemical bonds (due by May 13^th)

Exercise 3: Modular representation of reactions (due by May 23^th)

Exercise 4: Proteins (due by May 30^th)

Exercise 5: Quantities (due by June 6^th)

Exercise 6: Enzymes (due by June 20^th)

Exercise 7: Regulatory Circuits (due by July 4^th)

Administrative Stuff:

Requirements and Grading:

· Exercises: Weekly. Write and execute pi-calculus programs - 60%

- The best six submission of each student will be considered for the final grade.

- The grade of each exercise will mostly refer to correctness, though other aspects such as clarity and submission will be considered.

· Project: Model and analyze by simulation a larger system (other formats or types of projects can also be considered upon early approval) - 40%

o Projects should be conducted by interdisciplinary groups of up to 3 students or non-interdisciplinary groups of up to 2 students.

o A typical submission will include:

- A short presentation of the question that motivates the study.

- A short description of the model underlying the simulation.

- The output/s of the simulation presented in comprehendible form.

- A short account explaining the essence of the results and how they enlighten the motivating question.

- The ‘source’ of the simulation and instructions how to ’use’ it.

o To make sure the planned project meets the course's requirements, please, be sure to get approval for the project in advance from the course staff.

o The projects should be submitted by e-mail.

o Deadline for projects submission is August 31^st.

Syllabus:

In this course we will learn how to model, program, and simulate biochemical and molecular processes using computer science tools developed originally for the specification of concurrent computer processes. The course will include frontal lectures, programming/simulation exercises, and a final multidisciplinary team project. Topics:

1. An introduction to modeling molecular systems as concurrent systems

2. Modeling and simulation of coupled chemical reactions: pi-calculus and stochastic pi-calculus, Gillespie's Monte-Carlo algorithm.

3. Biochemistry: modular models for enzymatic reactions, compartmentalization and transport. Metabolic pathways

4. Molecular machines: polymerization reactions, transcription and translation as stochastic processes

5. Regulatory networks and signal transduction pathways: molecular and modular approaches

Registration:

If you are considering attending this course (even not for credits), please assist us by sending e-mail to Barak Shenhav, with the following details:

· Last name

· First Name

· E-mail

· Faculty and department

· M.Sc. / Ph.D. / other

· Credit / Free student

Thanks for your collaboration.

Pre-requisites:

· Some programming background (e.g. 'Introduction to CS' or any undergraduate level programming course).

· An introductory level course in molecular biology is recommended.

· Attendance of last year's course by Barkai and Alon is an asset but not required.

Useful Stuff:

Links

· The Biospi Project homepage.

Downloads

· The Biospi manual - Appendices

Books

· Communication and mobile systems: The pi-calculus, Robin Milner, Cambridge University Press, 1999.

· Molecular Biology of the Cell (3rd edition), Alberts et al., Garland Publishing Inc., 1994.

· Essential Cell Biology, Alberts et al., Garland Publishing Inc., 1998.

· University Chemistry (4th edition), Mahan and Myers, Addison-Wesley, 1987 (chapters 2, 6 and 9).

· Chemistry, Change R., McGraw-Hill, 1991 (chapters 3.1, 9 and 13).

· Fundamentals of Biochemistry, Voet D, Voet J.G. and Pratt C. W, Wiley and Sons, 1999.

Papers

· Gillespie D.T. (1976) A general method for numerically simulating the stochastic time evolution of coupled chemical reactions. Journal of Computational Physics 22: 403-434.

· Gillespie D. T. (1977) Exact stochastic simulation of coupled chemical reactions. Journal of physical chemistry 81: 2340-2361.

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Last updated on 5 July 2001