Introduction to Biocomputing

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Introduction to Biocomputing

• Bioinformatics, Biomolecular simulation, protein
  modeling

From biophysics and databases to protein and
membrane properties.
http//www.biochem.oulu.fi/Biocomputing/juffer/Tea
ching/Biocomputing/
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Overview of course

• Biomolecular simulation techniques Basic
  principles.
• Structural Bioinformatics Special subjects.
• Protein and membrane modeling Real applications.
• Examination Article presentations
• Two papers to read.

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Requirements

• Knowledge of physical chemistry
• Thermodynamics, chemistry.
• Knowledge of protein structures
• Protein structure.
• Knowledge of mechanics
• Concept of potential and kinetic energy.
• Concept of force.

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Biocomputing (1)

• New scientific discipline.
• Only in the 1990s the importance of Biocomputing
  has been realized
• Genome project (bioinformatics).
• Finland
• Several research groups, including Oulu, Turku,
  Tampere and Kuopio
• Increasingly higher chances for employment in
  this sector.

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Biocomputing is multidisciplinary
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Biocomputing (3)

• Bioinformatics
• proteomics
• data mining
• sequence alignment
• analysis genome sequence data

• Biomolecular
• simulation
• ligand affinity calculation
• protein and membrane dynamics
• protein function, enzymatic action
• electrostatics

• Protein modeling
• protein structure prediction (threading
  techniques, homology building)
• Ligand modelling, docking

Physics
Database, Statistics
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Computer simulation

• A simulation models or emulates on a single
  computer or on a collection of computers, the
  behavior of a given biological process with the
  objective to predict various quantitative
  properties.
• A simulation is an imitation of some real thing,
  state of affairs, or process. The act of
  simulating something generally entails
  representing certain key characteristics or
  behaviors of a selected physical or abstract
  system.
• Advanced computer programs can simulate weather
  conditions, electronic circuits, chemical
  reactions, atomic reactions, even biological
  processes.

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Drug discovery
Drug discovery in the next millenium
Target identification
After Ohlstein et al., Annu. Rev. Pharmacol.
Toxicol. 40, 177, 2000
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List of topics (1)

• Biomolecular simulation techniques
• Hierarchical modeling ? Different levels of
  description.
• Statistical thermodynamics.
• Molecular dynamics.
• Brownian dynamics.
• Monte Carlo.
• Energy minimization techniques.
• And more

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Theoretical Enzymology
Quantum chemistry/Molecular mechanics (fs).
Protein dynamics
Molecular dynamics (ps to ns).
Interfacial processes
Coarse-grained dynamics (µs to ms).
Protein translation
Stochastic modeling (ms to s).
Tumor growth
Multiple scale modeling (months to years).
Larger length and longer time scales. Less
molecular detail.
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Simulation of ribosome motion along mRNA
Protein adsorption
Concentrate on behavior
Peroxisomal import mechanism
Tumor growth
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List of topics (2)

• Structural bioinformatics
• Protein ligand design.
• Protein structure prediction
• Homology building.
• Threading.
• Ab Initio prediction.
• Protein engineering.
• And more

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List of topics (3)

• Protein and membrane modeling
• Protein dynamics.
• Free energy calculations
• Protein-ligand affinity.
• pKa calculations and electrostatics.
• Protein engineering.
• Solvent effects.
• Membrane simulations.
• Simulation of protein folding.
• And more

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Mathematics, Physics

• Quantitative way of explanation
• Basic calculus.
• Qualitative way of explanation
• Not always satisfactory.