Tertiary Structure Modeling (Homology, Threading, Ab Initio), Molecular Docking & CATH/SCOP Classifications - Bioinformatics | Agrigyan

• Ab Initio (De Novo) Protein Structure Prediction:
• Statements 1, 2, and 4 correctly describe ab initio prediction:
• Assumes the thermodynamic hypothesis (Anfinsen's dogma) that native protein structure corresponds to the global free energy minimum determined solely by amino acid sequence.
• Can be applied when no homologous structural templates exist in the PDB.
• Statement in Option 3: The ab initio prediction method attempts to produce protein structure based on sequence information along with the aid of known structure of its homologous proteins as template. $\implies$ NOT true.
• Using known structures of homologous proteins as templates is the definition of Homology Modeling (Comparative Modeling), the exact antithesis of ab initio modeling.
• Conclusion: Option 3 is not true.

Correct option: (3) The ab initio prediction method attempts to produce protein structure based on sequence information along with the aid of known structure of its homologous proteins as template.

• Computational Molecular Docking and AutoDock:
• Statement (I): Molecular docking is a computational method through which it is possible to predict interactions between two structures, which may be between a protein and a ligand or between two proteins. $\implies$ True.
• Predicts preferred binding poses and binding affinities (free energy of binding, $\Delta G_{\text{bind}}$).
• Statement (II): AutoDock is a computational docking program based on an empirical free energy force field and rapid Lamarckian genetic algorithm search method. $\implies$ True.
• AutoDock (developed by Olson laboratory at Scripps) utilizes a semi-empirical free energy force field calibrated on known complexes and employs the Lamarckian Genetic Algorithm (LGA) for conformational search space exploration.
• Conclusion: Both Statement (I) and Statement (II) are true (Option 1).

Correct option: (1) Both Statement (|) and Statement (II) are true.