Question

Some methods for computationally predicting protein structure from a sequence involve a combination of the “homology modeling” approach and “ab initio” techniques such as fragment assembly. Describe how both evolutionary data and knowledge of physico-chemical principles can be helpful when predicting the structure adopted by a protein sequence.

Answer 1

Ans : Using evolutionary data - The sequence of the protein of which the 3D structure is to be predicted is part of an evolutionary related family of sequences that are presumed to have essentially the same fold. Evolutionary variation in the sequences is constrained by a number of requirements including the maintainance of favourable interactions in direct residue - residue contacts . The inverse problem of protein fold prediction from particular sequence exploits pair corelations in the multiple sequence alignment to deduce which residue pairs are likely to be close to each other in the three dimensional structure. A subset of the predicted residue contact pairs is subsequently used to fold up any protein in the family into a approximate predicted 3D shape, which is then refined using standard molecular physics techniques, yeilding a predicted all atom 3D structure of the protein of interest.

Physico chemical principles - In this process protein fragments are assembled according to their physico chemical similarities using information extracted from known protein structures. Properties of amino acids such as hydrophobicity, polarity and charge are used to determine structure. Then a distance map is produced which provides information about structure of protein.