Homology-based approaches

Secondary structure prediction assigns a local helical (alpha) or extended (beta) structure to amino acid chains. The problem has been approached in an ab initio manner [46-48] for some time and many prediction methods have been developed based on properties of amino acids. Major advances have been achieved by employing homology-based approaches to 2D prediction. Such methods using sequence family information or consensus formation from several prediction methods are discussed in Section 6.4.1. 

We searched for isoprenyl diphosphate synthase gene sequences in P. abies using a homology-based approach. First, RNA was isolated from bark and wood of methyl jasmonate-treated spruce saplings from a single clone. This was then used as a template for reverse transcriptase PCR carried out with degenerate primers... 

ABSTRACT. A priori prediction of the 3-D stmcture of proteins remains an important unsolved problem. Of the theoretical methods employed today, only homology-based model building produces protein structures of sufficient accuracy to be of use in structure-fimction and related studies. The present work provides a discussion of the features of protein structure which bear on homology-based model building in addition to a detailed description of the homology-based approach, with examples drawn from our own work. 

More detailed aspects of protein function can be obtained also by force-field based approaches. Whereas protein function requires protein dynamics, no experimental technique can observe it directly on an atomic scale, and motions have to be simulated by molecular dynamics (MD) simulations. Also free energy differences (e.g. between binding energies of different protein ligands) can be characterised by MD simulations. Molecular mechanics or molecular dynamics based approaches are also necessary for homology modelling and for structure refinement in X-ray crystallography and NMR structure determination. 

The MTHFRs of Arabidopsis and maize have recently been cloned by genomics-based approaches, based on homology with the enzymes from other organisms.17 Like mammalian MTHFRs, the plant enzymes were found to be homodimers of two-domain subunits that are homologous to the mammalian enzymes throughout both domains. However, when the recombinant plant proteins were expressed in yeast, they were found to differ radically from the mammalian MTHFRs in both their pyridine nucleotide preference and their regulatory properties plant enzymes prefer NADH to NADPH, and they are insensitive to AdoMet.17... 

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