Technical interview guide

Structural Bioinformatics & Protein Structure Prediction

Predicting and validating 3D protein structure from sequence — homology modeling, deep-learning methods like AlphaFold, and how confident a predicted structure actually is.

Read: 49 min
Practice MCQs: 25
Interview QA: 25
Edition: v4
Editorial status: Reviewed
Relevant for: Computational Biologist

Scope: PDBx/mmCIF v5 and wwPDB validation; AlphaFold and AlphaFold DB guidance; ModelCIF; DSSP, MolProbity, TM-align and comparative-modeling source literature reviewed 2026-09-04.

Interview QA

Treat each question like a live interview question: answer out loud first (structure, assumptions, tradeoffs), then open the model answer to spot gaps and rehearse a tighter follow-up.

Curated: 2026-10-05 · Written: 2026-10-05 · Reviewed: 2026-10-04

QA-1

Design and defend a structural analysis for resolution.

QA-2

How do X-ray crystallography, Cryo-EM, and NMR differ when resolving flexible loops, multi-state conformational ensembles, and membrane proteins?

QA-3

Design and defend a structural analysis for occupancy and B factors.

QA-4

How does multiple sequence alignment depth and diversity impact co-evolutionary contact prediction, and how does Evoformer process these alignments compared to classic direct coupling analysis?

QA-5

Design and defend a structural analysis for alternate locations.

QA-6

Design and defend a structural analysis for missing residues.

QA-7

Design and defend a structural analysis for biological assemblies.

QA-8

Design and defend a structural analysis for PDBx/mmCIF parsing.

QA-9

Design and defend a structural analysis for sequence-coordinate mapping.

QA-10

Design and defend a structural analysis for Ramachandran validation.

QA-11

Design and defend a structural analysis for clashscore.

QA-12

Design and defend a structural analysis for ligand validation.

QA-13

Design and defend a structural analysis for RMSD.

QA-14

Design and defend a structural analysis for TM-score.

QA-15

Design and defend a structural analysis for comparative modeling.

QA-16

How do you select and validate structural templates for homology modeling versus deep learning approaches like AlphaFold, and how do sequence identity, coverage, and conformational state impact model quality?

QA-17

How is pLDDT calculated in AlphaFold, what structural characteristics correspond to low versus high scores, and why is it not an absolute measure of thermodynamic stability?

QA-18

Design and defend a structural analysis for predicted aligned error.

QA-19

Design and defend a structural analysis for intrinsic disorder.

QA-20

Design and defend a structural analysis for interfaces and multimers.

QA-21

Design and defend a structural analysis for docking.

QA-22

Design and defend a structural analysis for mutation effects.

QA-23

Design and defend a structural analysis for computed-model provenance.

QA-24

Design and defend a structural analysis for structure validation.

QA-25