Quantitative chemical structure and activity relationship

A.A. 2016/2017
Insegnamento per
10
Crediti massimi
88
Ore totali
SSD
BIO/10 CHIM/08
Lingua
Inglese

Struttura insegnamento e programma

Edizione attiva
Responsabile
Moduli o unità didattiche
Methods of analysis applied to water, air, biological fluids, tissues, food and In Silico Methods in Toxicology
CHIM/08 - CHIMICA FARMACEUTICA - CFU: 5
Lectures: 40 ore

Structural Bioinformatics
BIO/10 - BIOCHIMICA - CFU: 5
Laboratory individual activity: 16 ore
Lectures: 32 ore
Docente: Eberini Ivano

Prerequisiti e modalità di esame
The course requires the knowledge of base notions of mathematics, chemistry, biochemistry and molecular biology, which are needed for a proficient comprehension of the lessons. The examination consists of an oral discussion about two different structural bioinformatics topics and about two scientific papers related to the course subjects.
Methods of analysis applied to water, air, biological fluids, tissues, food and In Silico Methods in Toxicology
Programma
1. General principles of molecular modeling
1. File formats for storing chemical structures (pdb, mol2, smiles)..
2. Graphic representation of chemical structures
3. Force fields
4. Conformational analysis
5. Energy minimization
2. Ligand based drug design (LBDD)
1. Pharmacophore modeling
2. Molecular Alignment
3. Molecular interaction fields
4. QSAR and 3D-QSAR from structure to biological effects
5. Real implementations of LBDD methods
6. Applications
3. Structure based drug design (LBDD)
1. Docking
2. Scoring Functions
3. Real implementation of docking algorithms and scoring functions
4. Applications
4. Molecular dynamics
1. General principles and equations
2. Methods for integrating motion equations
3. Regulation of temperature and pressure
4. Methods for describing the solvent effects
5. Protein ligand affinity calculations
1. Approximated free energy methods (MMPBSA, LIE)
2. Free energy calculations (Metadynamics, Steered MD)
Materiale didattico e bibliografia
· Practical Bioinformatics by Michael Agostino - Garland Science
· Molecular Modeling (Principles and applications) of A. R Leach, ed Pretentice Hall.
· Molecular Modeling: Basic Principles and Applications by Hans-Dieter Holtje and Gerd Folkers, ed. Wiley.
Structural Bioinformatics
Programma
1. Introduction to Bioinformatics and Sequence Analysis

2. Introduction to Internet Resources
1. The NCBI and ENTREZ
2. PubMed
3. Gene Name Evolution
4. OMIM
5. Retrieving Nucleotide Sequences
6. Searching Patents
7. Public Grants Database: NIH RePORTER
8. Gene Ontology
9. The Gene Database
10. UniGene
11. The UniGene Library Browser

3. Introduction to the BLAST Suite and BLASTN
1. What is BLAST
2. BLAST Search
3. BLAST Results
4. BLASTN Across Species
5. BLAST Output Format

4. Protein BLAST: BLASTP
1. Codons and the Genetic Code
2. Amino Acids
3. BLASTP and the Scoring Matrix
4. BLASTP Search
5. Pairwise BLAST

5. Cross-Molecular Searches: BLASTX and TBLASTN
1. Messenger RNA Structure
2. cDNA
3. BLASTX
4. TBLASTN
6. Advanced Topic in BLAST
1. Reciprocal BLAST: Confirming Identities
2. Adjusting BLAST Parameters
3. Exon Detection
4. Repetitive DNA
5. Interpreting Distant Relationships

7. Bioinformatics Tools for the Laboratory
1. Restriction Mapping and Genetic Engeneering
2. Finding Open Reading Frame
3. PCR and Primer Design Tools
4. Measuring DNA and Protein Composition
5. The Sequence Retrieval System (SRS)
6. DotPlot

8. Protein Analysis
1. Finding Functional Patterns
2. Annotating an Unknown Sequence
3. Looking at Three-Dimensional Protein Structures
4. The Impact of Sequence on Structure
5. Building Blocks: A Multiple Domain Protein
6. Post-translational Modifications
7. Transmembrane Domain Detection

9. From Structure to Function: Protein Structure Prediction and Validation
1. Ligand::protein interaction
2. Mutagenesis
3. About Sampling of Conformational Space

10. Practical Examples
1. Comparative Modelling, High-throughput Screening and modulation of a class-A GPCR
2. Comparative Modelling, High-throughput Screening and chemical inhibition of an enzyme

11. Exploration of Short Nucleotide Sequences
1. Transcription Factor Binding Sites
2. Translation Initiation: The Kozak Sequence
3. Viewing Whole Genes
4. Exon Splicing
5. Polyadenylation Signals

12. MicroRNAs and Pathway Analysis
1. miRNA Function
2. miRNA Nomenclature
3. miRNA Families and Conservation
4. Structure and Processing of miRNAs
5. miRBase: The Repository for miRNAs
6. Linking miRNA Analysis to a Biochemical Pathway
7. KEGG: Biological Networks
8. TarBase: Experimentally Verified miRNA Inhibition

13. Multiple Sequence Alignments
1. Multiple Sequence Alignments Through BLAST
2. Clustal W
3. Modifying Clustal W Parameters
4. Comparing Clustal W, MUSCLE, and COBALT
5. Isoform Alignment Problem: Internal Splicing
6. Aligning Paralog Domains
7. I moduli
8. Manually Editing a Multiple Sequence Alignment

13. Browsing the Genome
1. Chromosomes
2. Synteny
Materiale didattico e bibliografia
· Practical Bioinformatics by Michael Agostino - Garland Science
· Molecular Modeling (Principles and applications) of A. R Leach, ed Pretentice Hall.
· Molecular Modeling: Basic Principles and Applications by Hans-Dieter Holtje and Gerd Folkers, ed. Wiley.
Periodo
Primo semestre
Periodo
Primo semestre
Modalità di valutazione
Esame
Giudizio di valutazione
voto verbalizzato in trentesimi
Siti didattici
Docente/i
Ricevimento:
Su appuntamento
Dipartimento di Scienze Farmacologiche e Biomolecolari, Via Giuseppe Balzaretti, 9 - 20133 Milano