Molecular modeling

Skills

  • Working with biological systems: structure, protein functional dynamics, macromolecular interactions
  • Evaluating molecular interactions with force fields:
    • Bonded interactions
    • Non-bonded interactions
    • Cross terms
    • Polarizable and reactive force fields
  • Computing with molecular mechanics:
    • Solvation: implicit/explicit solvation, water models
    • Potential energy surface:
      • Energy minimization: steepest-descent, conjugate gradient, Newton-Raphson
      • Molecular dynamics
      • Monte-Carlo simulations
  • Extracting properties with statistical mechanics:
    • Normal Mode Analysis
    • Binding affinity:
      • MM/PBSA
      • FEP

Tools

Amber16, CHARMM, Wordom, PLANTS, VMD

Context

Lectures and practicals:

  • "Molecular Simulations" by Rachel Schurhammer
  • "Biostructure and Modeling" by Marco Cecchini and Roland Stote

Chemoinformatics

Skills

  • Using and storing molecular structure representations on a computer
  • Calculating structural and physicochemical descriptors:
    • Molecular properties: energy, geometry, surface
    • Topological indices
    • Autocorrelation descriptors
    • ISIDA and CATS fragment descriptors
    • Molecular fields: CoMFA
  • Designing QSAR/QSPR classification and regression models:
    • Development: data curation, feature normalisation/scaling, feature selection, machine-learning methods
    • Validation: chance correlation, preparation of training and test sets, N-fold cross-validation
    • Application: applicability, reliability, and decidability domains
  • Operating a virtual screening campaign: Ligand-based and Structure-based approaches
    • Filters:
      • ADME (oral bioavailability): Lipinski, Veber
      • Structural alerts: toxicity, reactivity, PAINs
      • Synthetic feasibility
    • Similarity: structure, shape, field
    • QSAR
    • Pharmacophore
    • Docking: AutoDock Vina, PLANTS
    • Interaction Fingerprints
  • Integrating and managing a chemical database:
    • Structural search: exact match, substructural search (fingerprints, molecular graphs), similarity search
    • Chemical reaction search: exact match, substructural search, similarity search, condensed graph of reaction
    • Markush structures: chemistry patents, combinatorial chemistry
    • Database creation: relational model, InstantJChem
  • Analyzing similarity and diversity:
    • Fingerprints
    • Descriptors
    • 3D alignment: FlexS, ROCS, Pharmacophore
    • Clustering: hierarchical, k-means, MaxMin, Sphere exclusion
  • Visualizing a chemical space:
    • Graph-based: Scaffolds, Maximal Commom Substructures, Matched Molecular Pairs
    • Descriptor-based: Activity cliffs, Chemical Space Networks, Principal Component Analysis, Self Organizing Maps (Kohonen Neural Networks), Generative Topographic Mapping, t-distributed Stochastic Neighbor Embedding
  • Performing computer-aided synthesis design:
    • Retrosynthetic analysis: prediction of reactants
    • Reaction mechanism elucidation
    • Reaction outcome prediction

Tools

  • Schrödinger: Maestro 11
  • ChemAxon: MarvinView, MarvinSketch, Standardizer, InstantJChem
  • ISIDA
  • Jatoon

Context

Lectures and practicals

  • "Chemoinformatics 1", "Chemoinformatics 2" and "In Silico Chemical Diversity" by Alexandre Varnek, Hanoch Senderowitz, Igor Baskin, João Aires de Sousa

Drug design

Skills

  • Understanding molecular recognition: binding affinity of protein-ligand complexes, non-bonded interactions
  • Studying protein structures: sequence - structure - function relationship
  • Detecting and examining binding sites
  • Designing pharmacophores
  • Performing docking experiments

Tools

MOE (Molecular Operating Environment, Chemical Computing Group)

Context

Lectures and practicals:

  • "Structure-Based Computer-Aided Drug Design" by Esther Kellenberger

Drug discovery

Skills

  • Apprehending the stages in drug development: research, production, preclinical and clinical trials, marketing, drug safety monitoring
  • Establishing strategies in hit identification: rational drug design, screening
  • Performing hit to lead optimization: improving potency, bioavailability, patentability, toxicity

Context

Lectures:

  • "Drug Discovery" by Marcel Hibert, Line Bourel, Catherine Vonthron, Marie-Claude Kilhoffer

Quantum chemistry

Skills

  • Understanding the concepts behind the variational principle:
    • Hartree-Fock approximation
    • Configuration interaction
    • Multi-Configurational Self-Consistent Field
  • Interpreting the concepts behind non-variational methods:
    • Many-Body Perturbation Theory
    • Coupled Cluster
  • Comprehending Density Functional Theory
  • Applying second quantization

Context

Lectures and practicals:

  • "Advanced Quantum Chemistry" by Emmanuel Fromager
  • "Quantum Chemistry" by Vincent Robert

Organic chemistry

Skills

  • Studying organic chemistry reactions and mechanism: alcanes, alkenes, alkynes, halogen derivatives, alcohols, epoxydes, ethers, thiols, thioethers, amines, aldehydes, ketones, carboxylic acids, arenes
  • Understanding nucleophilic substitution (SN1, SN2), β-elimination (E1, E1CB, E2), aromatic substitution

Context

Lectures and practicals:

  • "Systematic Organic Chemistry" by Nadia Patino
  • "Organic Chemistry" by Nicolas Giuseppone

Inorganic chemistry

Skills

  • Studying transition metals
  • Understanding the coordination of tetrahedral and octahedral complexes
  • Comprehending the effects of weak/strong field - high/low spin
  • Producing Orgel and Tanabe-Sugano diagrams

Context

Lectures and practicals:

  • "Inorganic Chemistry" by Jean-Pierre Le Ny

Thermodynamics

Skills

  • Calculating thermodynamic quantities at the standard state: chemical potential, entropy, enthalpy
  • Studying chemical equilibrium and temperature influence on real solutions using the activity coefficient
  • Predicting the kinetic/thermodynamic reaction control

Context

Lectures:

  • "Kinetics and thermodynamics" by Remi Barillon

Chemical kinetics

Skills

  • Formulating rate laws from experimental results
  • Analyzing the reaction rate of complex reactions and coupled reactions: enzymatic catalysis, gas phase reactions, chained reactions, excited states kinetics

Context

Lectures and practicals:

  • "Kinetics of complex systems" by Thomas Ebbesen
  • "Kinetics and thermodynamics" by Remi Barillon

Material chemistry

Skills

  • Metals: understanding the extraction and processing techniques, the properties, the crystallographic structure and defects of metals, alloys and their phase diagrams.
  • Ceramics: naming the structure, synthesis procedures, and the properties of ceramic materials.
  • Polymers: comprehending the structure and properties of polymeric materials.

Context

Lectures:

  • "Materials - Introduction" by Sylvie Ferlay, Nathalie Viart and Gero Decher

Spectroscopy

Skills

  • Understanding the theory and approximations behind IR, UV, Raman, vibrational, rotational, ro-vibrational, NMR and mass spectroscopies.
  • Interpreting spectra using absorption and chemical shift tables.
  • Elucidating a structure from spectra.

Context

Lectures and practicals:

  • "Optical spectroscopies" by Petra Hellwig and Roberto Marquardt
  • "NMR spectroscopy and structural elucidation" by Burkhard Bechinger
  • "Cross-disciplinary practicals" by Quentin Raffy, Matthias Pauly, Aurelie Guenet, Véronique Bulach, Laurent Raibaut, Jordi Rull Barrull

Electrochemistry

Skills

  • Balancing redox reactions and predicting their spontaneity
  • Understanding how electrochemical cells and batteries work
  • Describing the main methods to prevent corrosion

Context

Lectures and practicals:

  • "Electrochemistry" by Petra Hellwig
  • "Electrochemistry" by Hervé Michel