BIO-INFORMATICA
2025-2026
SCHAKELJAAR BIOCHEMIE EN BIOTECHNOLOGIE
Lowie Boels
,Bio-informatica Lowie Boels
MODULE 1............................................................................................................................................................ 4
1. DATASTORAGE ......................................................................................................................................................... 4
2. GESCHIEDENIS ........................................................................................................................................................ 4
3. MENSELIJK GENOOM ................................................................................................................................................. 4
4. BIO-INFORMATICA VS. COMPUTATIONELE BIOLOGIE .......................................................................................................... 5
5. BIOINFORMATICA IN HET CENTRALE DOGMA ..................................................................................................................... 5
6. BIOINFORMATICA IS BOOMING...................................................................................................................................... 5
7. WELKE VELDEN IN BIO-INFORMATICA?............................................................................................................................ 6
MODULE 2:........................................................................................................................................................... 7
1. VAN SEQUENTIE NAAR STRUCTUUR EN FUNCTIE ................................................................................................................. 7
2. AMINOZUREN .......................................................................................................................................................... 7
3. STRUCTUUR VAN EIWITTEN .......................................................................................................................................... 8
De Primaire Structuur ........................................................................................................................................... 8
De Secundaire Structuur ....................................................................................................................................... 9
De Tertiaire Structuur............................................................................................................................................ 9
De Quaternaire Structuur & Interacties ................................................................................................................ 10
Metaalbinding .................................................................................................................................................... 10
MODULE 3:......................................................................................................................................................... 11
1. DATABASE ............................................................................................................................................................ 11
2. SEQUENTIE DATABASES ............................................................................................................................................ 11
3. HET FASTA FORMAAT ............................................................................................................................................. 12
MODULE 4:......................................................................................................................................................... 13
METHOD 1: SINGLE CRYSTAL X-RAY DIFFRACTION (CRYSTALLOGRAPHY) .................................................................................. 13
METHOD 2: PROTEIN NMR SPECTROSCOPY ..................................................................................................................... 15
METHOD 3: CRYO-ELECTRON MICROSCOPY (CRYO-EM) ..................................................................................................... 16
ADVANTAGES AND DISADVANTAGES ................................................................................................................................ 17
MODULE 5:......................................................................................................................................................... 18
1. INTRODUCTION TO THE PROTEIN DATA BANK (PDB) ........................................................................................................ 18
2. THE CLASSIC PDB FORMAT....................................................................................................................................... 18
General Information and Publication ................................................................................................................... 18
Refinement Statistics ......................................................................................................................................... 18
Sequence and Content ....................................................................................................................................... 18
Secondary Structure and Crystal Information ....................................................................................................... 18
Structural Coordinates ....................................................................................................................................... 19
Connections and Limitations .............................................................................................................................. 19
3. SPECIFIC ATOM PROPERTIES ..................................................................................................................................... 19
4. THE TRANSITION TO MMCIF / PDBX ............................................................................................................................ 20
MODULE 6:......................................................................................................................................................... 21
1. THE HISTORICAL EVOLUTION OF MOLECULAR VISUALIZATION............................................................................................. 21
2. THE CPK COLOR SCHEME AND PHYSICAL MODELS ......................................................................................................... 21
3. STRUCTURAL VISUALIZATION STYLES............................................................................................................................ 21
4. ADVANCED SURFACE REPRESENTATIONS ...................................................................................................................... 22
MODULE 7:......................................................................................................................................................... 23
1. PROTEIN STRUCTURAL ANALYSIS AND QUALITY CONTROL ................................................................................................. 23
2. COMPARING STRUCTURES IN 3D ................................................................................................................................ 24
3. FOLDS, DOMAINS, AND MOTIFS ................................................................................................................................. 25
4. TOPOLOGY AND FOLD DATABASES .............................................................................................................................. 26
5. STRUCTURE PREDICTION (THE FOLDING PROBLEM) ......................................................................................................... 27
MODULE 8:......................................................................................................................................................... 28
1
,Bio-informatica Lowie Boels
1. BASIC SEQUENCE ANALYSIS ...................................................................................................................................... 28
2. PATTERN DETECTION AND AI ..................................................................................................................................... 28
3. SECONDARY STRUCTURE PREDICTION ......................................................................................................................... 28
4. ALGORITHMS FOR SECONDARY STRUCTURE PREDICTION .................................................................................................. 29
The Chou-Fasman Algorithm (1970) .................................................................................................................... 29
The GOR Algorithm (1978) ................................................................................................................................... 29
Modern Approaches ........................................................................................................................................... 29
MODULE 9:......................................................................................................................................................... 30
1. EVOLUTION BY GENE DUPLICATION ............................................................................................................................. 30
2. THE THREE PATHWAYS OF DUPLICATED GENES .............................................................................................................. 30
Pathway A: Gene Dosage .................................................................................................................................... 30
Pathway B: Specialization ................................................................................................................................... 30
Pathway C: Neofunctionalization ........................................................................................................................ 30
Pathway D: Multidomain Proteins ........................................................................................................................ 31
3. TERMINOLOGY FOR EVOLUTIONARY RELATIONSHIPS ........................................................................................................ 31
4. EVOLUTION BY DIRECT MUTATION ............................................................................................................................... 31
5. MUTATION TYPES AND SEQUENCE ALIGNMENT ............................................................................................................... 31
MODULE 10: ....................................................................................................................................................... 33
1. SEQUENCE ALIGNMENT AND EVOLUTION ...................................................................................................................... 33
2. DOT-PLOTS (DOT-MATRIX) ....................................................................................................................................... 33
3. ALIGNMENT METRICS AND SUBSTITUTION MATRICES ........................................................................................................ 33
4. PAM (POINT ACCEPTED MUTATIONS) MATRICES ............................................................................................................ 34
5. BLOSUM (BLOCK SUBSTITUTION MATRIX) ................................................................................................................... 34
6. CHOOSING BETWEEN PAM AND BLOSUM ................................................................................................................... 35
MODULE 11: ....................................................................................................................................................... 36
1. THE NEED FOR AUTOMATED SEQUENCE ALIGNMENT ........................................................................................................ 36
2. THE NEEDLEMAN-WUNSCH ALGORITHM (GLOBAL ALIGNMENT) ......................................................................................... 36
Gap Penalties and NW Limitations ...................................................................................................................... 36
4. THE SMITH-WATERMAN ALGORITHM (LOCAL ALIGNMENT) ................................................................................................. 37
5. APPLICATIONS IN NEXT-GENERATION SEQUENCING (NGS) ............................................................................................... 37
MODULE 12: ....................................................................................................................................................... 38
1. THE CORE CONCEPT OF BLAST ................................................................................................................................. 38
2. THE BLAST ALGORITHM ........................................................................................................................................... 38
3. THE E-VALUE ......................................................................................................................................................... 39
4. BLAST PROGRAMS AND READING FRAMES ................................................................................................................... 40
5. INTERPRETING BLAST OUTPUTS ................................................................................................................................. 40
6. ADVANCED BLAST VARIATIONS ................................................................................................................................. 41
MODULE 13: ....................................................................................................................................................... 42
1. MULTIPLE SEQUENCE ALIGNMENT (MSA) ..................................................................................................................... 42
2. SEQUENCE LOGOS ................................................................................................................................................. 42
Shannon entropy ................................................................................................................................................ 43
4. PERFORMING THE ALIGNMENT: THE PROGRESSIVE APPROACH (CLUSTAL) ........................................................................... 44
5. ALTERNATIVE MSA ALGORITHMS ................................................................................................................................ 44
6. DERIVING CO-EVOLUTION AND 3D STRUCTURES FROM MSA............................................................................................. 45
MODULE 14: ....................................................................................................................................................... 47
1. FOUNDATIONS OF PHYLOGENETICS ............................................................................................................................. 47
The Concept and History..................................................................................................................................... 47
Anatomy of a Tree ............................................................................................................................................... 47
2. EVOLUTION OF TREE CONSTRUCTION: MORPHOLOGY VS. SEQUENCES................................................................................. 47
Handmade Morphological Trees.......................................................................................................................... 47
2
, Bio-informatica Lowie Boels
Sequence-Based Trees ....................................................................................................................................... 48
3. TREE FORMATS AND THE MOLECULAR CLOCK ................................................................................................................ 48
Visual Formats ................................................................................................................................................... 48
The Molecular Clock Theory ................................................................................................................................ 49
4. THE MATHEMATICS OF TREE TOPOLOGIES ..................................................................................................................... 49
Calculating Possible Combinations ..................................................................................................................... 49
Defining the Root ................................................................................................................................................ 50
5. THE 5 STAGES OF PHYLOGENETIC ANALYSIS .................................................................................................................. 50
Method A: Distance-Based (Clustering) ............................................................................................................... 51
Method B: Optimality-Based (Heuristic) ............................................................................................................... 51
6. APPLICATIONS AND CASE STUDIES .............................................................................................................................. 52
MODULE 15: ....................................................................................................................................................... 54
1. MOLECULAR MECHANICS (MM) VS. QUANTUM CHEMISTRY ............................................................................................... 54
2. CALCULATING ENERGY: THE TWO MAIN COMPONENTS .................................................................................................... 54
1. Bonded Interactions ....................................................................................................................................... 54
2. Non-Bonded Interactions ................................................................................................................................ 55
3. FORCE FIELDS (FF) ................................................................................................................................................. 56
4. THE POTENTIAL ENERGY SURFACE (PES) ...................................................................................................................... 56
5. APPLICATIONS OF BIOMOLECULAR MODELLING .............................................................................................................. 57
MODULE 16: ....................................................................................................................................................... 58
1. STRUCTURE PREDICTION ........................................................................................................................................... 58
2. HOMOLOGY MODELLING .......................................................................................................................................... 58
3. FOLD RECOGNITION ................................................................................................................................................ 59
4. ALPHAFOLD & ARTIFICIAL INTELLIGENCE ...................................................................................................................... 60
3
2025-2026
SCHAKELJAAR BIOCHEMIE EN BIOTECHNOLOGIE
Lowie Boels
,Bio-informatica Lowie Boels
MODULE 1............................................................................................................................................................ 4
1. DATASTORAGE ......................................................................................................................................................... 4
2. GESCHIEDENIS ........................................................................................................................................................ 4
3. MENSELIJK GENOOM ................................................................................................................................................. 4
4. BIO-INFORMATICA VS. COMPUTATIONELE BIOLOGIE .......................................................................................................... 5
5. BIOINFORMATICA IN HET CENTRALE DOGMA ..................................................................................................................... 5
6. BIOINFORMATICA IS BOOMING...................................................................................................................................... 5
7. WELKE VELDEN IN BIO-INFORMATICA?............................................................................................................................ 6
MODULE 2:........................................................................................................................................................... 7
1. VAN SEQUENTIE NAAR STRUCTUUR EN FUNCTIE ................................................................................................................. 7
2. AMINOZUREN .......................................................................................................................................................... 7
3. STRUCTUUR VAN EIWITTEN .......................................................................................................................................... 8
De Primaire Structuur ........................................................................................................................................... 8
De Secundaire Structuur ....................................................................................................................................... 9
De Tertiaire Structuur............................................................................................................................................ 9
De Quaternaire Structuur & Interacties ................................................................................................................ 10
Metaalbinding .................................................................................................................................................... 10
MODULE 3:......................................................................................................................................................... 11
1. DATABASE ............................................................................................................................................................ 11
2. SEQUENTIE DATABASES ............................................................................................................................................ 11
3. HET FASTA FORMAAT ............................................................................................................................................. 12
MODULE 4:......................................................................................................................................................... 13
METHOD 1: SINGLE CRYSTAL X-RAY DIFFRACTION (CRYSTALLOGRAPHY) .................................................................................. 13
METHOD 2: PROTEIN NMR SPECTROSCOPY ..................................................................................................................... 15
METHOD 3: CRYO-ELECTRON MICROSCOPY (CRYO-EM) ..................................................................................................... 16
ADVANTAGES AND DISADVANTAGES ................................................................................................................................ 17
MODULE 5:......................................................................................................................................................... 18
1. INTRODUCTION TO THE PROTEIN DATA BANK (PDB) ........................................................................................................ 18
2. THE CLASSIC PDB FORMAT....................................................................................................................................... 18
General Information and Publication ................................................................................................................... 18
Refinement Statistics ......................................................................................................................................... 18
Sequence and Content ....................................................................................................................................... 18
Secondary Structure and Crystal Information ....................................................................................................... 18
Structural Coordinates ....................................................................................................................................... 19
Connections and Limitations .............................................................................................................................. 19
3. SPECIFIC ATOM PROPERTIES ..................................................................................................................................... 19
4. THE TRANSITION TO MMCIF / PDBX ............................................................................................................................ 20
MODULE 6:......................................................................................................................................................... 21
1. THE HISTORICAL EVOLUTION OF MOLECULAR VISUALIZATION............................................................................................. 21
2. THE CPK COLOR SCHEME AND PHYSICAL MODELS ......................................................................................................... 21
3. STRUCTURAL VISUALIZATION STYLES............................................................................................................................ 21
4. ADVANCED SURFACE REPRESENTATIONS ...................................................................................................................... 22
MODULE 7:......................................................................................................................................................... 23
1. PROTEIN STRUCTURAL ANALYSIS AND QUALITY CONTROL ................................................................................................. 23
2. COMPARING STRUCTURES IN 3D ................................................................................................................................ 24
3. FOLDS, DOMAINS, AND MOTIFS ................................................................................................................................. 25
4. TOPOLOGY AND FOLD DATABASES .............................................................................................................................. 26
5. STRUCTURE PREDICTION (THE FOLDING PROBLEM) ......................................................................................................... 27
MODULE 8:......................................................................................................................................................... 28
1
,Bio-informatica Lowie Boels
1. BASIC SEQUENCE ANALYSIS ...................................................................................................................................... 28
2. PATTERN DETECTION AND AI ..................................................................................................................................... 28
3. SECONDARY STRUCTURE PREDICTION ......................................................................................................................... 28
4. ALGORITHMS FOR SECONDARY STRUCTURE PREDICTION .................................................................................................. 29
The Chou-Fasman Algorithm (1970) .................................................................................................................... 29
The GOR Algorithm (1978) ................................................................................................................................... 29
Modern Approaches ........................................................................................................................................... 29
MODULE 9:......................................................................................................................................................... 30
1. EVOLUTION BY GENE DUPLICATION ............................................................................................................................. 30
2. THE THREE PATHWAYS OF DUPLICATED GENES .............................................................................................................. 30
Pathway A: Gene Dosage .................................................................................................................................... 30
Pathway B: Specialization ................................................................................................................................... 30
Pathway C: Neofunctionalization ........................................................................................................................ 30
Pathway D: Multidomain Proteins ........................................................................................................................ 31
3. TERMINOLOGY FOR EVOLUTIONARY RELATIONSHIPS ........................................................................................................ 31
4. EVOLUTION BY DIRECT MUTATION ............................................................................................................................... 31
5. MUTATION TYPES AND SEQUENCE ALIGNMENT ............................................................................................................... 31
MODULE 10: ....................................................................................................................................................... 33
1. SEQUENCE ALIGNMENT AND EVOLUTION ...................................................................................................................... 33
2. DOT-PLOTS (DOT-MATRIX) ....................................................................................................................................... 33
3. ALIGNMENT METRICS AND SUBSTITUTION MATRICES ........................................................................................................ 33
4. PAM (POINT ACCEPTED MUTATIONS) MATRICES ............................................................................................................ 34
5. BLOSUM (BLOCK SUBSTITUTION MATRIX) ................................................................................................................... 34
6. CHOOSING BETWEEN PAM AND BLOSUM ................................................................................................................... 35
MODULE 11: ....................................................................................................................................................... 36
1. THE NEED FOR AUTOMATED SEQUENCE ALIGNMENT ........................................................................................................ 36
2. THE NEEDLEMAN-WUNSCH ALGORITHM (GLOBAL ALIGNMENT) ......................................................................................... 36
Gap Penalties and NW Limitations ...................................................................................................................... 36
4. THE SMITH-WATERMAN ALGORITHM (LOCAL ALIGNMENT) ................................................................................................. 37
5. APPLICATIONS IN NEXT-GENERATION SEQUENCING (NGS) ............................................................................................... 37
MODULE 12: ....................................................................................................................................................... 38
1. THE CORE CONCEPT OF BLAST ................................................................................................................................. 38
2. THE BLAST ALGORITHM ........................................................................................................................................... 38
3. THE E-VALUE ......................................................................................................................................................... 39
4. BLAST PROGRAMS AND READING FRAMES ................................................................................................................... 40
5. INTERPRETING BLAST OUTPUTS ................................................................................................................................. 40
6. ADVANCED BLAST VARIATIONS ................................................................................................................................. 41
MODULE 13: ....................................................................................................................................................... 42
1. MULTIPLE SEQUENCE ALIGNMENT (MSA) ..................................................................................................................... 42
2. SEQUENCE LOGOS ................................................................................................................................................. 42
Shannon entropy ................................................................................................................................................ 43
4. PERFORMING THE ALIGNMENT: THE PROGRESSIVE APPROACH (CLUSTAL) ........................................................................... 44
5. ALTERNATIVE MSA ALGORITHMS ................................................................................................................................ 44
6. DERIVING CO-EVOLUTION AND 3D STRUCTURES FROM MSA............................................................................................. 45
MODULE 14: ....................................................................................................................................................... 47
1. FOUNDATIONS OF PHYLOGENETICS ............................................................................................................................. 47
The Concept and History..................................................................................................................................... 47
Anatomy of a Tree ............................................................................................................................................... 47
2. EVOLUTION OF TREE CONSTRUCTION: MORPHOLOGY VS. SEQUENCES................................................................................. 47
Handmade Morphological Trees.......................................................................................................................... 47
2
, Bio-informatica Lowie Boels
Sequence-Based Trees ....................................................................................................................................... 48
3. TREE FORMATS AND THE MOLECULAR CLOCK ................................................................................................................ 48
Visual Formats ................................................................................................................................................... 48
The Molecular Clock Theory ................................................................................................................................ 49
4. THE MATHEMATICS OF TREE TOPOLOGIES ..................................................................................................................... 49
Calculating Possible Combinations ..................................................................................................................... 49
Defining the Root ................................................................................................................................................ 50
5. THE 5 STAGES OF PHYLOGENETIC ANALYSIS .................................................................................................................. 50
Method A: Distance-Based (Clustering) ............................................................................................................... 51
Method B: Optimality-Based (Heuristic) ............................................................................................................... 51
6. APPLICATIONS AND CASE STUDIES .............................................................................................................................. 52
MODULE 15: ....................................................................................................................................................... 54
1. MOLECULAR MECHANICS (MM) VS. QUANTUM CHEMISTRY ............................................................................................... 54
2. CALCULATING ENERGY: THE TWO MAIN COMPONENTS .................................................................................................... 54
1. Bonded Interactions ....................................................................................................................................... 54
2. Non-Bonded Interactions ................................................................................................................................ 55
3. FORCE FIELDS (FF) ................................................................................................................................................. 56
4. THE POTENTIAL ENERGY SURFACE (PES) ...................................................................................................................... 56
5. APPLICATIONS OF BIOMOLECULAR MODELLING .............................................................................................................. 57
MODULE 16: ....................................................................................................................................................... 58
1. STRUCTURE PREDICTION ........................................................................................................................................... 58
2. HOMOLOGY MODELLING .......................................................................................................................................... 58
3. FOLD RECOGNITION ................................................................................................................................................ 59
4. ALPHAFOLD & ARTIFICIAL INTELLIGENCE ...................................................................................................................... 60
3
