GBCB 5874

GBCB5874: Problem Solving in GBCB - Spring 2007

Mon 2.30 - 5.15 pm LITRV 1800

"Everything that the living things do ... can be described as the wiggling and jiggling of atoms" R. Feynman

Instructor:        David Bevan
Office:              201 Fralin Biotechnology Center
Phone:              (540)231-5040 (E-mail is strongly preferred)
Email:               drbevan@vt.edu
Office Hours:   By appointment

Instructor:        Alexey Onufriev
Office:              2160C Torgersen Hall
Phone:              (540)231-4237 (E-mail is strongly preferred)
Email:               alexey@cs.vt.edu
Office Hours:    just drop by any afternoon.
Text Books:

Structural Bioinformatics (SB) , by Philip E. Bourne and Helge Weissig (Strongly recommended)

Syllabus

Class Picture.

Classes:

Date Tasks / Discussion Topics Presenter(s) Papers(s) Recommended reading

Jan 22 (1) Introduction
(2) Brief description of the projects Bevan, Onufriev N/A N/A

Jan 29 Finalizing assignment of the projects
(1) The basics of protein structure
(2)The basics of nucleic acid structure
(3) Visualization Onufriev
Bevan H++ description (depending on project choices) SB pp. 15-41, 41-75

Feb 5 (1) Protein Folding Onufriev ... SB, pp. 135-159
Feb 12 (1) The Nature of Interdisciplinary Research Bevan Facilitating Interdisciplinary Research ...
Feb 19 Project/Literature review. 35 mins per group + 5 mins questions from the class. (1) ALL GROUPS ... ...
Feb 26 Homology modeling

QSAR

Docking
Bevan N/A SB, pp 509-523

SB, pp 443-476

Mar 12 1) Ab initio protein structure prediction
2) Computational Prediction of Folding Rates
3) Drug Discovery
1) Tim
2) Shenghua
3) Bevan (1) B. Kuhlman, G. Dantas, G. C. Ireton, G. Varani, B. L. Stoddard, D. Baker, Design of a Novel Globular Protein Fold with Atomic-Level Accuracy , Science, 302, 1364-1368, 2003. [No ned to go into every gory detail of every algorithm used, just give us a general idea + key results ]
(2) Plaxco et al. Contact order, transition state placement and the refolding rates of single domain proteins , J. Mol. Biol. 277, 985-994 (1998) [No need to present the whole thing, focus on the folding rate <-> contact order correlation]
SB, pp 499-509, 547-558
Mar 19 Discussion of class projects. ... ... ...
Mar 26 (1) Rob

(2) Song

Discussion of Class Projects ... (1)Morris et al. Real spherical harmonic expansion coefficients as 3D shape descriptors for protein binding pocket and ligand comparisons. , Bioinformatics 10, 2347-2355 (2005) (This is a MUST-DO, see Homeworks. Talk to Onufriev about how to present this paper. )

(2) Kamb et al. (2007) Why is Cancer Drug Discovery so Difficult? Nature Rev. Drug Disc. 6: 115-120. ...
Apr 2 Introduction to Proteomics

Discussion of Class Projects Helm, 2:30 - 4:00 pm

... ...
Apr 9 (1) Jason
(2) Lakshmi
(3) Discussion of class projects 15 mins each group ... ...
Apr 16 (1) Teeraphan
(2) Joe
(3) Discussion of class projects 15 mins each group ... ...
Apr 23 Understanding bacterial evolution through ortholog alignments Setubal, 4.00 - 5.15 pm ... ...
Apr 30 Class projects: Report critiques ... ... ...

All presentations

All papers

Papers for 2007

Listed below are papers that can be used for presentations. Select your paper and let us know if there are any dates on which you cannot do your presentation. We will then add your name and paper to the schedule. The idea is that each of you will have presented at least one paper by the end of this class.

Cho et al. (2006) The Application of Systems Biology to Drug Discovery. Curr. Opin. Chem. Biol. 10: 294-302. [Teeraphan]

Payne et al. (2007) Drugs for Bad Bugs: Confronting the Challenges of Antibacterial Discovery. Nature Rev. Drug Disc. 6: 29-40. [Jason]

Kamb et al. (2007) Why is Cancer Drug Discovery so Difficult? Nature Rev. Drug Disc. 6: 115-120. [Song]

Rostami-Hodjegan and Tucker (2007) Simulation and Prediction of in vivo Drug Metabolism in Human Populations from in vitro Data. Nature Rev. Drug Disc. 6: 140-148.

Terfloth and Gasteiger (2001) Neural Networks and Genetic Algorithms in Drug Design. Drug Disc. Today 6 (Suppl. 2) 102-108.

Geldenhuys et al. (2006) Optimizing the Use of Open-source Software Applications in Drug Discovery. Drug Disc. Today 11: 127-132. [Joe]

Ptytsin al. Non-functional conserved residues... J. Mol. Biol. [Lakshmi]

Class Projects, Research Groups and initial guidelines:

Life and Death: Advice for NIH -- Shenghua Li, Teeraphan Laomettachit Guidelines

Computational Gene Silencing -- Rob StClair, Lakshmi Dharmarajan Guidelines

Functional Wormholes in Proteins -- Joe Ruscio, Zhuo Song Guidelines

Comparing Protein Structures -- Tim Driscoll, Jason Rodriguez Guidelines

Homeworks (individual work required of each student):

HW 0 (warm up). Due Feb 5 in class. HINT: If you missed the relevant lecture, use the SB book or the web.

HW 1. Due April 9 in class HINT: You need to understand the main idea of the Plaxco et al. paper to answer the questions.

HW 2. Due April 16 in class HINT: You need to understand the main ideas of the Morris et al. paper to answer the questions.

Resources:

Example Presentations:

De Novo Protein Design

Final Report:

Final report template (PDF)
Latex and support files for the report template.
A good intro into LaTex
Free, cross-platform GUI LaTex editor

Useful Web Sites

The Protein Data Bank
Some basics of computational prediction of RNA secondary structure
GSL -The GNU Scientific Library - Development Page
Protein structure completion and pK prediction
MOLPROBITY: X-ray Structure refinement
VIENNA: RNA Secondary Structure Prediction
Some discussion about Molecular Surface, Solvent Accessible surface, related algorithms and software

Date	Tasks / Discussion Topics	Presenter(s)	Papers(s)	Recommended reading
Jan 22	(1) Introduction (2) Brief description of the projects	Bevan, Onufriev	N/A	N/A
Jan 29	Finalizing assignment of the projects (1) The basics of protein structure (2)The basics of nucleic acid structure (3) Visualization	Onufriev Bevan	H++ description (depending on project choices)	SB pp. 15-41, 41-75
Feb 5	(1) Protein Folding	Onufriev	...	SB, pp. 135-159
Feb 12	(1) The Nature of Interdisciplinary Research	Bevan	Facilitating Interdisciplinary Research	...
Feb 19	Project/Literature review. 35 mins per group + 5 mins questions from the class. (1)	ALL GROUPS	...	...
Feb 26	Homology modeling QSAR Docking	Bevan	N/A	SB, pp 509-523 SB, pp 443-476
Mar 12	1) Ab initio protein structure prediction 2) Computational Prediction of Folding Rates 3) Drug Discovery	1) Tim 2) Shenghua 3) Bevan	(1) B. Kuhlman, G. Dantas, G. C. Ireton, G. Varani, B. L. Stoddard, D. Baker, Design of a Novel Globular Protein Fold with Atomic-Level Accuracy , Science, 302, 1364-1368, 2003. [No ned to go into every gory detail of every algorithm used, just give us a general idea + key results ] (2) Plaxco et al. Contact order, transition state placement and the refolding rates of single domain proteins , J. Mol. Biol.* 277, 985-994 (1998)* [No need to present the whole thing, focus on the folding rate <-> contact order correlation]	SB, pp 499-509, 547-558
Mar 19	Discussion of class projects.	...	...	...
Mar 26	(1) Rob (2) Song Discussion of Class Projects	...	(1)Morris et al. Real spherical harmonic expansion coefficients as 3D shape descriptors for protein binding pocket and ligand comparisons. , Bioinformatics 10, 2347-2355 (2005) (This is a MUST-DO, see Homeworks. Talk to Onufriev about how to present this paper. ) (2) Kamb et al. (2007) Why is Cancer Drug Discovery so Difficult? Nature Rev. Drug Disc. 6: 115-120.	...
Apr 2	Introduction to Proteomics Discussion of Class Projects	Helm, 2:30 - 4:00 pm	...	...
Apr 9	(1) Jason (2) Lakshmi (3) Discussion of class projects	15 mins each group	...	...
Apr 16	(1) Teeraphan (2) Joe (3) Discussion of class projects	15 mins each group	...	...
Apr 23	Understanding bacterial evolution through ortholog alignments	Setubal, 4.00 - 5.15 pm	...	...
Apr 30	Class projects: Report critiques	...	...	...