Chapter 1ঃProperties and structure of macromolecules
Atomic and Molecular Forces in Macromolecules
The structural integrity of biological macromolecules is governed by a delicate interplay of
energetic interactions. While covalent bonds (energy ~200-800 kJ/mol) provide the chemical
backbone, the biological "function" is dictated by non-covalent forces (energy ~1-30 kJ/mol).
Electrostatic Interactions (Coulombic Forces): These occur between permanently charged
groups. In proteins, "salt bridges" form between carboxylate groups (COO^-) of acidic amino
acids and amino groups (NH_3^+) of basic ones. These are highly dependent on the dielectric
constant of the medium (water vs. protein interior).
Hydrogen Bonding: This is a specialized dipole-dipole attraction. In an alpha-helix, every
backbone carbonyl oxygen (C=O) forms a hydrogen bond with the backbone N-H group four
residues earlier. This Cooperativity makes the structure highly stable.
Van der Waals Forces: These are universal attractions between all atoms. They arise from
London dispersion forces (temporary dipoles). Although weak, the "sum" of thousands of these
interactions in a tightly packed protein core provides significant stability.
Hydrophobic Effect: This is the most dominant force in protein folding. Non-polar side chains
(like Leucine or Valine) cannot form H-bonds with water. To minimize the loss of entropy in the
surrounding water "clathrate" structures, these non-polar groups collapse into the center of the
molecule. This Entropic Drive is what forces a protein to fold into its native state.
Amino Acids and the Geometry of the Peptide Bond
Proteins are linear heteropolymers of alpha-amino acids. Each amino acid is "chiral" (except
glycine), meaning it exists in L and D isomeric forms; however, life exclusively uses the L-form.
The Peptide Bond (Amide bond) is the linkage between the alpha-amino group of one residue
and the alpha-carboxyl group of another. Biophysically, this bond is unique because the lone
pair of electrons on the Nitrogen is delocalized into the Carbonyl group. This creates a Partial
Double Bond Character, which has two major consequences:
The bond is Planar and cannot rotate.
The bond is almost always in the Trans configuration to avoid "Steric Hindrance" between side
chains.
The only flexibility in a protein chain comes from the single bonds on either side of the
alpha-carbon, known as the Dihedral Angles (phi and psi).
Hierarchical Levels of Protein Structure
Primary Structure: This is the specific sequence of amino acids determined by DNA. Even a
single change (mutation) here can cause diseases like Sickle Cell Anemia.
Secondary Structure: These are local spatial arrangements. The alpha-helix is a right-handed
coil where side chains point outward. The beta-pleated sheet consists of extended strands
(parallel or anti-parallel). These structures satisfy the hydrogen-bonding requirements of the
protein backbone.
Tertiary Structure: This represents the global "folding" of a single polypeptide. It is stabilized by
disulfide bridges (covalent S-S bonds between Cysteine residues), ionic bonds, and the
hydrophobic core.
Quaternary Structure: Many functional proteins consist of multiple polypeptide chains
(protomers). For example, Hemoglobin is a tetramer (alpha beta chains). This level allows for
Allostery, where the binding of a molecule to one chain changes the shape and affinity of the
other chains.
Nucleic Acid Architecture and DNA Stability
Nucleic acids are the information-carrying biopolymers. A Nucleotide consists of a Pentose
sugar, a Nitrogenous base, and a Phosphate group.
The DNA Double Helix: Two strands run in opposite directions (Anti-parallel). The exterior
consists of a negatively charged Sugar-Phosphate Backbone, which makes DNA highly soluble
in water. The interior contains the Nitrogenous bases.
Base Pairing: Adenine (A) pairs with Thymine (T) via 2 H-bonds; Guanine (G) pairs with
Cytosine (C) via 3 H-bonds. This makes G-C rich DNA more thermally stable.
Base Stacking: The flat, aromatic rings of the bases stack on top of each other. The pi-pi orbital
interactions between these stacks are actually more responsible for DNA's stability than the
H-bonds themselves.
RNA (Ribonucleic Acid): RNA contains a hydroxyl (-OH) group at the 2' position of the ribose
sugar. This makes RNA more susceptible to alkaline hydrolysis (breaking down) compared to
DNA, which is why DNA is the preferred molecule for long-term storage.
Genetic Information Flow: Transcription and Translation
Transcription: RNA Polymerase "unzips" the DNA and creates a complementary mRNA strand.
This occurs in the nucleus of eukaryotes.
The Genetic Code: This is a dictionary that relates the 4-letter language of DNA to the 20-letter
language of proteins. It is:
Triplet-based: 3 nucleotides = 1 Codon.
Non-overlapping: Each base is part of only one codon.
Degenerate: There are 64 possible codons but only 20 amino acids, so many amino acids are
coded by multiple codons (e.g., Leucine has 6).
Translation: This takes place in the Ribosome. Transfer RNA (tRNA) acts as the physical link.
One end of the tRNA has an Anticodon that matches the mRNA, and the other end carries the
corresponding Amino Acid.
Structural Analysis: X-Ray, NMR, and Spectroscopy
X-Ray Crystallography: This is the most powerful tool for structure determination. A protein is
grown into a crystal, and an X-ray beam is passed through it. The electrons in the atoms scatter
the X-rays, creating a Diffraction Pattern. By applying a Fourier Transform to the intensity and
phase of these spots, scientists can map the Electron Density and build an atomic model.
NMR (Nuclear Magnetic Resonance) Spectroscopy: Unlike X-ray, NMR can be done in solution,
mimicking natural physiological conditions. It relies on the "spin" of nuclei like ^1H, ^{13}C, or
^{15}N. By observing how these spins interact, we can calculate the distances between atoms
and observe how the protein "wiggles" or changes shape in real-time.
UV-Visible Spectroscopy: Used for quantification. Proteins show a sharp absorption peak at 280
nm due to the aromatic rings of Phenylalanine, Tyrosine, and Tryptophan. DNA/RNA absorb
strongly at 260 nm. The ratio of 260/280 is a standard lab test to check for sample purity.
chapter 2 : Neurobiophysics.
Overview of the Nervous System and Neural Communication
The nervous system is a complex biological network that processes and transmits information
through electrochemical signals. It is divided into the Central Nervous System (CNS) and the
Peripheral Nervous System (PNS). The fundamental functional unit is the Neuron.
Communication between neurons occurs at specialized junctions called Synapses. This
communication is a two-step process: Electrical (within the neuron via action potentials) and
Chemical (between neurons via neurotransmitters). The speed and efficiency of this system rely
on the biophysical properties of the neuronal membrane and the specialized proteins embedded
within it.
Basic Membrane Properties and Ion Channels
The neuronal membrane is a Phospholipid Bilayer that acts as both a Capacitor (storing charge)
and a Resistor (resisting the flow of ions). Because the lipid core is hydrophobic, ions cannot
pass through it directly.
Ion Selectivity: Selectivity is determined by the Selectivity Filter within the channel protein. This
filter uses precise atomic distances to strip the "hydration shell" off a specific ion (like K^+),
allowing it to pass while rejecting others (like Na^+) based on size and charge density.
Gating Mechanisms: Channels can be Voltage-gated (responding to changes in membrane
potential), Ligand-gated (responding to chemical binders), or Mechanosensitive.
Diffusion and Fick’s Law
The movement of ions across the membrane is driven by two gradients: the Concentration
Gradient and the Electrical Gradient.
Fick’s First Law of Diffusion states that the molar flux (J) is proportional to the concentration
gradient:
J = -D dc/dx, (ডিফারেন্সিয়েশন এর মতো করে লিখবা)
where D is the diffusion coefficient.
In neurobiology, we combine this with electrical forces in the Nernst-Planck Equation to describe
how ions move. This movement creates the Electrochemical Potential, which is the energy
source for all neural signaling.
Membrane Potential and the Resting State
The Resting Membrane Potential (V_m) is typically around -70 mV. This negative charge inside
the cell is maintained by:
Selective Permeability: The membrane is much more permeable to K^+ than to Na^+ at rest.
Ion Pumps: The Na^+/K^+ ATPase pump actively transports 3 Na^+ ions out for every 2 K^+
ions in, using ATP. This creates a "steady state" where the interior remains negatively charged.
Action Potential: Generation and Phases
An Action Potential is a rapid, "all-or-none" reversal of the membrane potential. It consists of
distinct biophysical phases:
Depolarization: When a stimulus reaches a Threshold (approx. -55 mV), voltage-gated Na^+
channels open rapidly. Na^+ rushes into the cell, driven by both concentration and electrical
gradients, making the interior positive (+30 to +40 mV).
Repolarization: Na^+ channels close (inactivate), and voltage-gated K^+ channels open. K^+
flows out of the cell, bringing the potential back toward negative.
Hyperpolarization: K^+ channels stay open slightly too long, making the potential more negative
than the resting state before stabilizing.
Propagation of Action Potential and Conduction Velocity
Once generated, the action potential must travel down the Axon. This occurs via local current
loops where the depolarization of one segment triggers the Na^+ channels in the adjacent
segment.
Conduction Velocity is determined by two physical factors: the Axoplasmic Resistance (R_a)
and the Membrane Capacitance (C_m).
To increase speed, biology either increases the axon diameter (decreasing R_a) or adds a
Myelin Sheath.
Conduction in Myelinated Nerve Fibers
Myelin is a fatty, insulating layer formed by Schwann cells or Oligodendrocytes. It acts by
increasing membrane resistance and decreasing capacitance.
Saltatory Conduction: The myelin sheath is interrupted at intervals called Nodes of Ranvier,
which contain a high density of Na^+ channels. The electrical signal "jumps" from one node to
the next. This is significantly faster and more energy-efficient than continuous conduction in
unmyelinated fibers.
Electrical Model of a Nerve Fibre
Physicists model the nerve fiber as a Cable Equation. The axon is treated as an electrical circuit
consisting of a series of resistors (the internal fluid) and parallel combinations of capacitors and
resistors (the membrane).
Length Constant (lambda): The distance over which a voltage change decays to 37% of its
maximum.
Time Constant (tau): How quickly the membrane charges or discharges. These constants
determine how well a neuron can "sum" signals from other neurons.
Equivalent Dipole and Volume Conductor Fields
When a group of neurons fires, they create a flow of current in the extracellular space. This can
be modeled as an Equivalent Dipole (a pair of equal and opposite charges).
Volume Conduction: The biological tissue surrounding the nerve acts as a Volume Conductor,
allowing the electrical field to be detected at a distance. This is the physical basis for EEG
(brain), ECG (heart), and EMG (muscle) recordings.
Neuromuscular Junction and Muscle Action Potential
The Neuromuscular Junction (NMJ) is the synapse between a motor neuron and a skeletal
muscle fiber.
Neurotransmitter Release: When the action potential reaches the nerve terminal, Ca^{2+}
enters, causing vesicles to release Acetylcholine (ACh).
ACh Binding: ACh binds to receptors on the muscle membrane (Sarcolemma), causing a
localized depolarization called the End-Plate Potential.
Muscle AP: If this potential is strong enough, it triggers a Muscle Action Potential, which travels
along the muscle fiber and leads to contraction via calcium release from the sarcoplasmic
reticulum.
Disorders and Clinical Biophysics
Demyelination: In diseases like Multiple Sclerosis (MS), the myelin is destroyed. This increases
membrane capacitance and causes the current to leak out, leading to a "conduction block"
where the signal dies out before reaching its destination.
Nerve Block: Pharmacological agents (like lidocaine) act as Sodium Channel Blockers. By
binding to the internal pore of the Na^+ channel, they prevent depolarization, effectively
"silencing" the nerve and preventing pain signals from reaching the brain.
Neuromuscular Disorders: Myasthenia Gravis is an example where the body attacks ACh
receptors at the NMJ, leading to failed transmission and profound muscle weakness.