* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Medical Physics and Statistics
Computational chemistry wikipedia , lookup
Electron configuration wikipedia , lookup
Halogen bond wikipedia , lookup
Artificial photosynthesis wikipedia , lookup
Metallic bonding wikipedia , lookup
Cation–pi interaction wikipedia , lookup
Electronegativity wikipedia , lookup
Bent's rule wikipedia , lookup
Water splitting wikipedia , lookup
Electrolysis of water wikipedia , lookup
Molecular orbital diagram wikipedia , lookup
Bond valence method wikipedia , lookup
Implicit solvation wikipedia , lookup
Physical organic chemistry wikipedia , lookup
Chemical biology wikipedia , lookup
Two-hybrid screening wikipedia , lookup
Proteolysis wikipedia , lookup
Photosynthetic reaction centre wikipedia , lookup
Protein–protein interaction wikipedia , lookup
Hydrogen bond wikipedia , lookup
Protein adsorption wikipedia , lookup
History of molecular biology wikipedia , lookup
Metalloprotein wikipedia , lookup
Atomic theory wikipedia , lookup
Resonance (chemistry) wikipedia , lookup
Hypervalent molecule wikipedia , lookup
History of molecular theory wikipedia , lookup
Semester Lectures Structural organization of biomolecules. Condensed matter. Liquid crystals, lipids. Biostatistics I. Biostatistics II. Ultrasound. Magnetic resonance imaging. Equilibrium thermodynamics. Transport phenomena. Miklós Kelermayer Diffusion, osmosis. Complexity Medical Physics and Statistics Blood circulation, cardiac function. Bioelectric processes. Sensory function. Vision and hearing. Biophysics of motion. Dimensions of Living Systems Thermodynamics 1023 Atoms 1010 Atoms Mesoscale 103 Atoms Quantum chemistry Quantum physics 101 Atoms 100 Atom Structural Organization of Biomolecules Types of bonds Atomic interactions According to location: intramolecular, intermolecular According to bond energy (“strength”): strong (primary), weak (secondary) repulsive interactions r = distance r0 = bond length Eb = bond energy (negative): Electronegativity (): ability of an atom to attract electrons towards itself in a covalent bond. Sum of ionization energy and electron affinity. [Linus Pauling (1901-1994), Nobel Prize (1954 chemistry, 1962 peace)] Difference of electronegativities equivalent to the (positive) energy to be invested for bond rupture. Interaction-free condition: Epot = 0 r= b attractive interactions E pot = E attr + E rep = A B + rn rm Covalent bond Sharing of pairs of electrons between atoms, or between atoms and other covalent bonds. Attraction-to-repulsion stability that forms between atoms when they share electrons. • Bond energy: several eV (strong). • Valence electrons contribute to molecular orbitals. • Molecular geometry determined by symmetry of atomic electron states. • Pure covalent bond is rare, electrostatic effects often arise. metallic ionic covalent primary bonds Sum of electronegativities Bonds Based on ChargeCharge Interactions Ionic bond Electrostatic interaction Bond energy: ~0.2 eV Polar covalent bond Bond energy: 2-3 eV Large difference between electronegativities Multi-ion crystals Dipole-dipole interaction Polar covalent bond Van der Waals interaction • Attractions between atoms, molecules, and surfaces (weak). • Caused by correlations in the fluctuating polarizations of nearby particles. • Dispersion forces, London forces. Hydrogen Bond • Attractive force between the hydrogen attached to an electronegative atom of one molecule and an electronegative atom of a different molecule. • Results from a dipole-dipole force with a hydrogen atom bonded to nitrogen, oxygen or fluorine Must not be confused with a covalent bond to hydrogen. • Energy: ~0.2 eV. rA, rB = van der Waals radii Jan Diderik van der Waals (1837-1923), Nobel prize 1910 Fritz London (1900-1954) Gecko foot stickiness: Bristles (setae) coupled in parallel Artificial gecko foot Snapshot from a simulation of liquid water. Intermolecular hydrogen bonding in a self-assembled dimer. Boltzmann Distribution News Headlines • Universal organizing principle in ensembles. • Describes the probability for the distribution of the states of a system. The first prize of the Idaho Falls High School Science Fair was awarded on April 26 to a student of Eagle Rock High School. The student wanted to demonstrate the extent to which the public is manipulated by vague references to science in generating environmental concern. He prepared a proposal for banning the use of the chemical dihydrogen monoxide and investigated whether he can convince supporters to sign it. He argued for the toxicity of the chemical based on the following: (Distribution of “microscopic states” across “macroscopic states”.) ni =e n0 • • • • • • Ludwig Boltzmann (1844-1906) • i 0 kB T i = energy sates 0 = lowest-energy state n0 = number of partices in the lowest-energy state ni = number of particles in the i energy state kB = Boltzmann’s constant (relates units of temperature to units of energy) T = absolute temperature N = total number of particles 1. the chemical induces strong perspiration and vomiting, 2. it is one of the main components of acid rain, 3. its gaseous form may cause serious burns, 4. its excessive inhalation may lead to suffocation, 5. it contributes to erosion, 6. it significantly reduces the efficiency of car brakes, 7. it has been shown to be present in cancer. The student surveyed 50 people for support of the proposal: Forty three (43) signed immediately. Six (6) asked for time to think. Only one (1) person knew that the chemical is water. . . Water • Only chemical that is liquid in nature Biophysics of water • Only chemical that naturally exists in all three states • Although inorganic, extremely important for LIFE, which is organic Structure of the water molecule I. One of the smallest molecules: barely larger than a single atom Structure of the water molecule II. • Tetrahedral structure • sp3 hybridization (Hybridization: combination of states with identical principal quantum number but different symmetry) Oxygen: 2s2p4 109.47˚ O H 0.96-0.99 Å (gas - ice) H Lone-pair, non-bonding electrons Structure of the water molecule III. Large constant dipole moment isolated molecule: + Structure of the water molecule IV. van der Waals radius: ~ 3.2 Å non-spherical shape 104.45˚ - Structure of the water molecule V. Rotational and vibrational motion of the water molecule Water dimer: H-bond between the proton and lone-pair electrons Absorption in the infrared and red spectral region -> “blue” color of natural waters Hydrogen bonding in water Formation of pentameric water Structure of ice • 9 different forms • Conventional ice: hexagonal structure • Coordination number: 4 (each molecule coordinates another four) Interstitium: could incorporate a water molecule Structure of liquid water H-bridge: cohesion + repulsion Cluster formation: bicyclo-octamer From clusters to networks: 280 molecules form icosahedral structure Physical properties of water I. Large dipole moment: Very good solvent Electrolyte solutions Anomalous densityTemperature function (g/cm3) 1.00 + Non-bonded interactions H-bonded interactions Spatial networks: May explain anomalous properties of water 4 Microwave oven! T (˚C) Life in the frozen lake! Physical properties of water II. Hydration Phase diagram • Phase curve: two pases are in equilibrium • Area between phase curves: a single phase is present • Cross-section: triple point P (kPa) melting point curve boiling point curve Electrolyte solutions 2. Non-electrolyte solutions, apolar molecules hydrophobic hydration 3. Protein hydration Maintenance of 3D structure Polarized “multilayers” 4. Nucleic acids Base pairing WATER ICE Bead exclusion by water multilayer? triple point 101 0.61 sublimation curve -273 1. 2 μm latex beads GAS Base pairing 0.0076 100 T (˚C) water Multilayer formation Nafion polymer Biological macromolecules are GIANT molecules Macromolecules DNS double helix DNA released from bacteriophage head Biological macromolecules are EXCITING molecules Proportion of macromolecules in the cell by mass is LARGE Ions, small molecules (4%) Phospholipids (2%) DNA (1%) 30 % other compounds RNA (6%) Proteins 15%) Newly synthesized protein (silk fibroin) Structure of hemoglobin subunit Bacterial cell Biological macromolecules: biopolyers Shape of polymers 1. Linear Polymers: chains built up from monomers 2. Branched Number of monomers: N>>1; Typically, N~102-104, but, in DNA, e.g.: N~109-1010 Biopolymer Polysaccharides (2%) 3. Circular Monomer Bond Protein Amino acid Covalent (peptide bond) Nucleic acid (RNA, DNA) Nucleotide (CTUGA) Covalent (phosphodiester) Polysaccharide (e.g., glycogen) Sugar (e.g., glucos) Covalent (e.g., -glycosidic) Protein polymer (e.g., microtubule) Protein (e.g., tubulin) Secondary Shape of polymer chain changes dynamically. Possible mechanisms: 1. Rotation around CC-bonds 2. Freely jointed chain (FJC) 3. Bending, wormlike chain (WLC) MACROMOLECULES 70 % Water Shape of the polymer chain resembles random walk Mechanics of polymers Entropic elasticity Brown-movement - “random walk” rN “Square-root law”: Thermal fluctuations of the polymer chain R = Nl = Ll 2 2 R Configurational entropy (orientational disorder of elementary vectors) increases. R = end-to-end distance N = number of elementary vectors l = ri = correlation length ri = elementary vector r1 Nl = L = contour length The chain shortens. l is related to bending rigidity. Biopolymer elasticity Visualization of biopolymer elasticity Tying a knot on a single DNA molecule l = correlation length L = contour length Rigid chain l >> L Microtubule microbead in moveable optical trap Phase contrast image Semiflexible chain l~L Flexible chain l << L Fluorescence image Actin filament microbead in stationary optical trap DNA Kinosita Group The peptide bond Protein folding Condensation reaction followed by the relase of water Display of protein structure Protein structure Primary Amino acid sequence Secondary Tertiary -helix -sheet -turn 3D structure of single-chain protein wireframe -helix: •right handed •3.4 residue/turn •H-bridges -sheet: •parallel or •antiparallel •H-bridges between distant residues backbone Myosin S-1 spacefilling ribbon Bonds holding protein structure together Protein structure classes 1. All alpha 1. Disulfide bridge: between cysteine residues calmodulin 2. All beta porin 2. Hydrogen bond: shared proton 3. Salt bridge: between oppositely charged residues 4. Hydrophobic interaction: between hydrophobic residues (in the interior of the molecule) (3. Alfa-beta) 4. Multidomain myosin Levinthal’s paradox: Levinthal’s paradox: Are all conformations explored by the protein molecule? Are all conformations explored by the protein molecule? Number of possible protein configurations: in Planar peptide group determined by the peptide bond i: number of configurations related to the amino acid n: number of amino acids „Folding funnel” Protein folding diseases Pathology: -Alzheimer’s disease, -Familial amyloidotic neuropathy (FAP) Methods of protein unfolding (denaturation) • • • Heat Chemical agent Mechanical force In the living cell, chaperones assist protein folding Force (pN) Mechanical unfolding of a single protein with atomic force microscope Beta-fibrils: Insoluble aggregates Mechanical unfolding of a betasheet protein Steps of computer-simulated domain unfolding 140 120 100 80 60 0.22 0.24 0.26 0.28 0.3 0.32 0.34 Extension (μm) Mechanical unfolding of titin I27 domain Mechanical stability provided by shear pattern of H-bond patch Force spectrum of I2712 Basis of mechanical stability: H-bridges between the first and last ß-strands of the domain Carrion-Vazquez et al. 2000 Mechanical unfolding of C2A domain Mechanical stability in proteins Principle of parallel bond coupling Low mechanical stability due to zipper pattern of H-bond patch Force spectrum of C2A9 Carrion-Vazquez et al. 2000 Gecko foot stickiness: Bristles (setae) coupled in parallel Artificial gecko foot