Introduction to Statistical Thermodynamics of Soft and Biological Matter Lecture 2 Statistical thermodynamics II • Free energy of small systems. • Boltzmann distribution. Partition function. • Probability distributions. Fluctuations. • Free energy of two-state system. • Kinetic interpretation of the Boltzmann distribution. Barrier crossing. • Unfolding of single RNA molecule. Some more soft and biological matter… Polymers Gels sol gel Polymers – linear macromolecules • Amphiphiles: soaps, lipids, membranes • polar head (love water) • hydrocarbon tail (hate water) Self-assembly And more biological matter… Actin in cell bilayer vesicle Cell on substrate Vesicle shapes Entropy… Molecules A Molecules B Probability of each state: Hard-sphere liquid Lower Entropy… Hard-sphere freezing is driven by entropy ! Higher Entropy… Hard-sphere crystal Entropy of ideal gas For one molecule: V – total volume - “cell” volume (quantum uncertainty ) For N molecules: Indistinguishablility Free energy of ideal gas: density: Pressure of ideal gas Free energy of ideal gas: N – number of particles V - volume density: Pressure: Osmotic forces: Protein solution Concentration difference induces osmotic pressure Semi-permeable membrane (only solvent can penetrate) Free energy For closed system: a Small system For open (small) system Free energy is minimized: Reservoir, T - Helmholtz free energy - Gibbs free energy Protein molecule with several possible conformations Free energy Free energy landscape: 2 M 1 3 Reaction coordinate (order parameter) Boltzmann distribution • System with many possible states (M possible states) (different conformations of protein molecule) Each state has probability Each state has energy Free energy (per one protein molecule): - normalization condition Constraint minimization • Minimize free energy with respect to : Constraint minimization Minimize free energy: Subject to constraint: Method of Lagrange Multipliers (look at any book on calculus): Lagrange multiplier Partition function Free energy: Minimize free energy. Solution: Substitute Partition function: into F: Sequence Analysis Course… Lecture 9 Boltzmann equation DNA/Protein structure-function analysis and prediction. Lecture 10… Self-Consistent Mean Field (SCMF) modeling The notion of probability distribution • Probability distribution function: - random variable - probability to find in the interval - normalization condition - average value of Fluctuation (variance): Examples of probability distributions Gaussian probability distribution: Your turn: find A variance: 2 Uniform probability distribution: 1.75 1.5 1.25 1 0.75 0.5 0.25 0.25 0.5 0.75 1 1.25 1.5 1.75 2 Example: fluctuations of spring in thermal bath - energy of spring verify: - probability distribution Equipartition theorem: Example: Two state system Kinetic interpretation of the Boltzmann distribution - activation barrier Detailed balance (at equilibrium): Number of molecules in state 2 and in state 1 Unfolding of single RNA molecule J. Liphardt et al., Science 292, 733 (2001) Optical tweezers apparatus: Two-state system and unfolding of single RNA molecule J. Liphardt et al., Science 292, 733 (2001) Extension Open state: Close state (force applied): force extension