136. Which one of the following protein structure prediction methods is based on the principle of locating lowest
energy minimum in the conformation space of a protein?
1. Ab initio structure prediction
2. Threading
3. Fold prediction
4. Homology modeling

Question

Which one of the following protein structure prediction methods is based on the principle of locating the lowest energy minimum in the conformation space of a protein?

1. Ab initio structure prediction

2. Threading

3. Fold prediction

4. Homology modeling

Detailed Explanation

Protein structure prediction is a fundamental challenge in bioinformatics, with various methods developed to predict the three-dimensional structure of proteins from their amino acid sequences. The principle of energy minimization plays a crucial role in many of these prediction methods, as proteins tend to fold into the structure with the lowest possible energy, often referred to as the native conformation.

Let’s break down the given options:

1. Ab initio structure prediction:

   • This method is based on energy minimization principles. The term ab initio means “from the beginning” or “from first principles.” In this approach, the protein’s three-dimensional structure is predicted by searching through the vast conformational space of possible protein structures. The goal is to locate the lowest energy state, which corresponds to the most stable structure of the protein.

   • This method involves computational simulations to explore different folding patterns and identify the most energetically favorable conformation.

2. Threading:

   • Threading, also known as fold recognition, involves aligning the target sequence to a template protein structure. It doesn’t rely solely on energy minimization but instead identifies a similar fold in a protein database, then refines the structure. Threading is useful when a homologous protein’s structure is known but doesn’t necessarily focus on energy minimization in the same way as ab initio methods.

3. Fold prediction:

   • Fold prediction involves predicting the general fold or structural class of a protein. It uses various algorithms and databases to determine which known protein fold is most likely to be adopted by the target sequence. It may use energy-based methods but is not focused on energy minimization to the same extent as ab initio methods.

4. Homology modeling:

   • Homology modeling, also known as comparative modeling, relies on the alignment of the target sequence with a known template protein structure. The structure of the homologous protein is then used as a model for predicting the structure of the target. While energy minimization is involved in refining the model, the main basis for this approach is sequence similarity rather than conformational energy minimization.

Correct Answer: 1. Ab initio structure prediction

• Ab initio structure prediction is the method that directly utilizes energy minimization to predict the protein structure by searching the conformational space for the lowest energy state. This method does not rely on known templates or sequence homology but instead tries to predict the most stable structure based purely on physical principles and computational methods.

Conclusion

The Ab initio structure prediction method is based on the principle of locating the lowest energy minimum in the conformation space of a protein. By exploring various possible folds and configurations, it aims to find the most energetically stable conformation of a protein, which is essential for understanding its biological function and interactions.