Reading Guides

Reading Guide

Biochemistry

October 2024

For the undergraduate level, with basic graduate level exploration.


How to use this guide

  • Do chemistry first.
  • Draw everything. Structures, reaction mechanisms, enzyme cycles, membranes, gene expression flows, metabolic pathways etc.
  • Do problems, not just reading.
  • Learn the lab bench. A genuine biochemistry education is incomplete without assays, gels, chromatography, cloning/PCR, spectroscopy, and data analysis.
  • Read papers after you do the core. Learn how the field actually argues.

Part 0: Mathematics, Physics, and Data

Calculus

Needed before: physical chemistry, kinetics, thermodynamics, quantitative biology.
Learn: derivatives, integrals, multivariable calculus, gradients, exponentials/logs, and basic differential equations.
Primary: James Stewart, Calculus, or Thomas, Thomas' Calculus.

Statistics and Data Analysis

Needed before: labs, genomics, enzymology, research papers.
Learn: distributions, error bars, confidence intervals, regression, nonlinear curve fitting, p-values, multiple testing, and reproducibility.
Primary: John Taylor, An Introduction to Error Analysis.
Biology/data option: Whitlock & Schluter, The Analysis of Biological Data.

Programming

Needed for: genomics, structural biology, image analysis, quantitative papers.
Learn: Python or R, plotting, data cleaning, sequence files, curve fitting, and basic statistics packages.
Primary: Python with NumPy/pandas/matplotlib, or R with tidyverse.

Physics

Needed before: physical/biophysical chemistry, spectroscopy, microscopy, structural biology.
Learn: mechanics, thermodynamics, electricity/magnetism, waves, optics, and basic quantum ideas.
Primary: Halliday, Resnick & Walker, Fundamentals of Physics, or Young & Freedman, University Physics.


Part 1: Chemistry Foundation

General Chemistry

Purpose: atomic structure, bonding, equilibrium, acid-base chemistry, thermodynamics, kinetics, and redox.
Primary: Zumdahl & Zumdahl, Chemistry, or Brown, LeMay, Bursten et al., Chemistry: The Central Science.
Use with: lab practice in measurement, titration, pH, spectroscopy, chromatography, and error analysis.

Organic Chemistry

Purpose: the language of biomolecular structure and reaction mechanism.
Learn: stereochemistry, substitution/elimination, carbonyl chemistry, aromaticity, radicals, pericyclic basics, protecting groups, and biological mechanisms.
Primary: David Klein, Organic Chemistry.
Deeper: Clayden, Greeves & Warren, Organic Chemistry.

Physical Chemistry

Purpose: the quantitative core behind binding, folding, membranes, metabolism, enzymes, and spectroscopy.
Learn: thermodynamics, chemical potential, statistical mechanics basics, kinetics, quantum chemistry, spectroscopy, and electrochemistry.
Primary: Atkins & de Paula, Physical Chemistry.
Biochemistry-focused alternative: Tinoco, Sauer, Wang, Puglisi, Harbison & Rovnyak, Physical Chemistry: Principles and Applications in Biological Sciences.

Analytical Chemistry and Instrumentation

Purpose: how biochemical claims are measured.
Learn: calibration, chromatography, mass spectrometry, UV-vis/fluorescence, NMR basics, electrophoresis, assay design, and uncertainty.
Primary: Daniel Harris, Quantitative Chemical Analysis.
Reference: Skoog, Holler & Crouch, Principles of Instrumental Analysis.


Part 2: Biology Foundation

Introductory Biology

Purpose: one full pass over cells, genetics, evolution, physiology, and molecular biology.
Primary: Campbell Biology.
Alternative: MIT OCW 7.01SC Fundamentals of Biology.

Genetics

Build on: intro biology.
Learn: Mendelian genetics, chromosomes, linkage, recombination, mutation, gene regulation, population genetics, genetic screens, and modern sequencing-based genetics.
Primary: Hartwell et al., Genetics: From Genes to Genomes.
Alternative: Pierce, Genetics: A Conceptual Approach.

Cell Biology

Build on: intro biology, biochemistry.
Learn: membranes, organelles, cytoskeleton, trafficking, signaling, cell cycle, apoptosis, extracellular matrix, and cellular organization.
Primary: Alberts et al., Molecular Biology of the Cell.
Gentler: Alberts et al., Essential Cell Biology.
Alternative: Lodish et al., Molecular Cell Biology.

Molecular Biology

Build on: intro biology, genetics, organic chemistry, core biochemistry.
Learn: DNA replication, repair, recombination, transcription, RNA processing, translation, regulation, chromatin, and experimental logic.
Primary: Watson et al., Molecular Biology of the Gene.
Alternative: Alberts or Lodish, above.


Part 3: Core Biochemistry

Biochemistry I: Structure, Enzymes, and Metabolism

Build on: general chemistry, organic chemistry, intro biology.
Learn: water, pH/buffers, amino acids, protein structure, enzymes, carbohydrates, lipids, membranes, nucleic acids, vitamins/cofactors, glycolysis, TCA cycle, oxidative phosphorylation, lipid metabolism, amino acid metabolism, nitrogen metabolism, and pathway regulation.
Primary: Berg, Tymoczko, Gatto & Stryer, Biochemistry.
Equally standard: Nelson & Cox, Lehninger Principles of Biochemistry.
Alternative: Voet, Voet & Pratt, Fundamentals of Biochemistry, or Miesfeld & McEvoy, Biochemistry.

Enzymology and Mechanism

Build on: organic chemistry, physical chemistry, core biochemistry.
Learn: Michaelis-Menten kinetics, inhibition, allostery, transition states, catalytic strategies, pH-rate profiles, isotope effects, and enzyme assay design.
Primary: Cornish-Bowden, Fundamentals of Enzyme Kinetics.
Reference: Fersht, Structure and Mechanism in Protein Science.

Metabolism and Regulation

Build on: core biochemistry.
Learn: energy charge, redox logic, flux, compartmentalization, hormonal control, fed/fasted state, metabolic disease, cancer metabolism, and experimental tracing.
Primary: Berg/Stryer or Lehninger metabolism chapters.
Deeper: Frayn, Metabolic Regulation: A Human Perspective.
Modern angle: read reviews on isotope tracing, metabolic flux analysis, and cancer metabolism.

Biophysical Chemistry

Build on: physical chemistry, calculus, core biochemistry.
Learn: binding equilibria, cooperative binding, protein folding, thermodynamic cycles, macromolecular interactions, membranes, diffusion, electrochemical gradients, kinetic models, and spectroscopy.
Primary: Tinoco et al., Physical Chemistry: Principles and Applications in Biological Sciences.
Alternative: Cantor & Schimmel, Biophysical Chemistry.

Structural Biology

Build on: biochemistry, biophysical chemistry.
Learn: protein domains, ligand binding, crystallography, NMR, cryo-EM, AlphaFold/model interpretation, structure validation, and molecular graphics.
Primary: Rupp, Biomolecular Crystallography.
For protein structure: Branden & Tooze, Introduction to Protein Structure.
Practical tools: PyMOL, ChimeraX, RCSB PDB, UniProt, AlphaFold DB.


Part 4: Laboratory and Research Methods

Core Biochemistry Lab

Learn: pipetting, buffers, pH, sterile technique, centrifugation, protein purification, chromatography, SDS-PAGE, Western blotting, ELISA, enzyme assays, spectrophotometry, fluorescence, and basic mass spectrometry.
Primary: Wilson & Walker, Principles and Techniques of Biochemistry and Molecular Biology.
Reference: Deutscher, Guide to Protein Purification.

Molecular Biology Lab

Learn: PCR, cloning, restriction enzymes, plasmids, bacterial transformation, gel electrophoresis, qPCR, sequencing, mutagenesis, reporter assays, and basic cell culture.
Primary: Green & Sambrook, Molecular Cloning: A Laboratory Manual.

Experimental Design

Learn: controls, replicates, blinding where relevant, positive/negative controls, dose-response curves, calibration, statistical power, and figure interpretation.
Primary: read the methods and figures of strong papers slowly. Reconstruct what experiment would falsify each claim.

Research Literature

Start with: review articles in Annual Review of Biochemistry, Nature Reviews Molecular Cell Biology, Trends in Biochemical Sciences, and Current Opinion journals.
Then: primary papers. For each paper, identify the question, method, main figure, strongest control, weakest assumption, and next experiment.


Part 5: Advanced Branches

Chemical Biology and Drug Discovery

Focus: using chemical tools to study and manipulate biological systems.
Learn: probes, inhibitors, bioorthogonal chemistry, chemical genetics, target engagement, medicinal chemistry basics, SAR, ADME, and resistance.
Primary: Miller & Tanner, Essentials of Chemical Biology.
Drug discovery: Patrick, An Introduction to Medicinal Chemistry, Silverman, The Organic Chemistry of Drug Design and Drug Action.

Molecular Genetics and Genomics

Focus: gene regulation and genome-scale measurement.
Learn: sequencing, chromatin, enhancers, transcription-factor binding, RNA-seq, ChIP-seq, CRISPR screens, single-cell genomics, and regulatory networks.
Primary: Watson et al., Molecular Biology of the Gene.
Computational: Pevzner, Computational Molecular Biology, or Compeau & Pevzner, Bioinformatics Algorithms.

Cell Signaling and Cancer Biology

Focus: how molecular circuits control cells and fail in disease.
Learn: receptors, kinases, phosphatases, second messengers, feedback, cell cycle, apoptosis, oncogenes, tumor suppressors, DNA damage, and targeted therapy.
Primary: Alberts, Molecular Biology of the Cell.
Cancer: Weinberg, The Biology of Cancer.

Immunology and Host–Pathogen Biology

Focus: molecular recognition, immune signaling, infection, and defense.
Learn: antibodies, T/B cells, innate immunity, antigen presentation, cytokines, vaccines, viral replication, bacterial pathogenesis, and immune disease.
Immunology primary: Murphy & Weaver, Janeway's Immunobiology.
Virology primary: Flint et al., Principles of Virology.

Systems, Synthetic, and Computational Biology

Focus: biological systems as networks, circuits, and programmable mechanisms.
Learn: gene circuits, feedback, network motifs, stochasticity, modeling, omics integration, synthetic circuits, and protein engineering.
Primary: Alon, An Introduction to Systems Biology.
Synthetic biology: Endy-style papers, iGEM project archives, and recent review articles.

Biotechnology and Protein Engineering

Focus: turning biochemical understanding into tools, drugs, diagnostics, and materials.
Learn: recombinant protein expression, directed evolution, display technologies, antibodies, enzymes, biologics, fermentation, purification, formulation, and quality control.
Primary: Walsh, Biopharmaceuticals: Biochemistry and Biotechnology.
Protein engineering: Branden & Tooze for structure, then review papers on directed evolution and protein design.


Suggested Order

  1. General Chemistry + Calculus.
  2. Introductory Biology + Organic Chemistry I.
  3. Organic Chemistry II + Biology lab basics.
  4. Physics + statistics/data analysis.
  5. Physical Chemistry or biophysical chemistry.
  6. Core Biochemistry: structure, enzymes, metabolism.
  7. Molecular Biology + Genetics.
  8. Cell Biology + upper-level lab methods.
  9. One advanced branch: structural biology, chemical biology, genomics, cancer/signaling, immunology/virology, systems/synthetic biology, or biotechnology.