https://pages.htgaa.org/2026a/siwei-zhang/homework/week-04-hw-protein-design-part-i/index.html🐉 Project Objective: Bacteriophage Engineering This document outlines the core learning experience and the collaborative framework designed to drive an optimized bacteriophage project. 1. Mastery of Basic Concepts Phage Biology: Understanding the lytic and lysogenic life cycles, and the structural modularity of viral components (Capsid, Tail, Baseplate). Synthetic Biology Framework: Introduction to the “Design-Build-Test-Learn” (DBTL) cycle in viral engineering. Therapeutic Potential: Exploring the role of phages in addressing antimicrobial resistance (AMR) and precision microbiome editing. 2. Amino Acid Structure & Biochemistry Chemical Taxonomy: Categorization of the 20 standard amino acids based on hydrophobicity, charge, and polarity. Side-Chain Interactions: Analyzing how hydrogen bonds, salt bridges, and disulfide bridges dictate protein stability. Conformational Constraints: Understanding the Ramachandran plot and the energetic landscape of protein folding. 3. 3D Protein Visualization & Analysis Software Proficiency: Hands-on training with professional-grade tools such as PyMOL, ChimeraX, or NGL Viewer. Structural Mapping: Visualizing surface electrostatic potentials, hydrophobicity, and potential binding pockets. Superimposition: Learning to align wild-type and mutant structures to assess structural deviations (RMSD). 4. Diversity of ML-based Design Tools Structure Prediction: Leveraging AlphaFold 3 or RoseTTAFold for high-accuracy 3D modeling of viral proteins. Fixed-Backbone Design: Using ProteinMPNN to redesign amino acid sequences for a specific structural scaffold. Generative Scaffolding: Implementing RFdiffusion for de novo design of receptor-binding motifs and functional binders. Sequence Modeling: Utilizing Protein Language Models (e.g., ESM-3) to predict the impact of specific mutations on protein function. 👩‍🦰 Part A: Fundamental Principles & Frontiers in Protein Engineering This section covers fundamental inquiries into biochemistry, evolutionary biology, and structural protein design.Hugoen