Summary of "Biophysical Chemistry 2018 - Lecture 1"

Summary of Biophysical Chemistry 2018 - Lecture 1

Instructor: Eric Lien Årnes, Professor of Biophysics at SCI Life Lab.
The course alternates between chemistry and physics topics, progressively layering concepts.
Emphasis on understanding basic chemistry and physics principles to interpret protein structure and function.
Central dogma highlighted: Sequence → Structure → Function.
Aim: Understand how amino acid sequences determine protein structure, which in turn determines function.

Amino acids are small molecules with a central alpha carbon, amino group, carboxyl group, hydrogen, and a variable R group.
They are zwitterionic (carry both positive and negative charges).
All amino acids (except glycine) are chiral; only L-amino acids are genetically encoded.
Chirality is fundamental to biological function and drug design.
Amino acids classified by size, polarity, charge, and special properties (e.g., cysteine, proline, glycine).
Importance of understanding amino acid properties rather than memorizing structures.

Genetic code redundancy: 64 codons encode 20 amino acids plus stop signals.
Codon frequency influences amino acid abundance.
Peptide bonds form via polymerization, creating heteropolymers (proteins made of different amino acids).
Frederick Sanger’s sequencing of insulin established the concept of unique protein sequences.

Proteins range from small (~100 residues) to very large (e.g., titin with 30,000 residues).
Proteins fold into unique 3D structures, stabilized by peptide bonds, hydrogen bonds, and other interactions.
Secondary structures:
Alpha helices: stabilized by hydrogen bonds every 4 residues.
Beta sheets: formed by hydrogen bonds between strands; can be parallel or antiparallel.
Folding driven by physics and free energy minimization.
Levinthal paradox: despite astronomical possible conformations, proteins fold rapidly, implying guided folding pathways.

X-ray crystallography:
Traditional method to determine atomic structures of proteins.
Requires protein crystals; challenging for membrane proteins.
Data interpreted via Fourier transforms and modeling.
Cryo-electron microscopy (cryo-EM):
Recent breakthrough allowing structure determination without crystallization.
Resolution improved dramatically, enabling visualization of side chains.
Revolutionized membrane protein structural biology.
Examples of Nobel Prize-winning work in protein and nucleic acid structure determination.

Importance of torsion (dihedral) angles Phi (φ) and Psi (ψ) in protein backbone conformation.
Ramachandran plots map allowed torsion angle regions; glycine and proline have distinct conformational preferences.
Protein folding and structure driven by interplay of:
Steric constraints (atom clashes)
Hydrogen bonding
Electrostatics (partial charges and dipoles)
Van der Waals forces
Alpha helices have a macrodipole due to aligned peptide bonds.
Electrostatic interactions are strong and long-range, crucial for protein stability and function.

Protein function depends on precise structure; mutations can disrupt function and cause disease.
Ion channels as an example: selectivity for potassium over sodium explained by physical chemistry principles (hydration shells, electrostatics).
Protein folding and stability linked to thermodynamics and free energy landscapes.

Future lectures will delve deeper into physics (free energy, Boltzmann distributions).
Emphasis on integrating physics and chemistry to understand biological function.
Encouragement to read classical papers to understand the scientific discovery process.
Study visits and practical sessions planned.
Importance of active participation and asking questions.