Origins of specificity and affinity in antibody-protein interactions
博士 === 國立陽明大學 === 生物醫學資訊研究所 === 102 === Antibodies from natural repertoire are able to recognize various protein surfaces and prefer in using aromatic residues, Tyr, Trp and to some less extent Phe, to interact with proteins. On the other hand, previous analyses of epitopes did not find clear prefer...
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| Format: | Others |
| Language: | en_US |
| Published: |
2014
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| Online Access: | http://ndltd.ncl.edu.tw/handle/29701729851944329147 |
| Summary: | 博士 === 國立陽明大學 === 生物醫學資訊研究所 === 102 === Antibodies from natural repertoire are able to recognize various protein surfaces and prefer in using aromatic residues, Tyr, Trp and to some less extent Phe, to interact with proteins. On the other hand, previous analyses of epitopes did not find clear preference of physicochemical properties. How these aromatic residues of paratopes interact with epitopes remains an unsettled question. Computational methods are proposed in this work to predict functional paratopes within structural paratopes and study their corresponding functional epitopes. Binding energy to antibody protein complexes is contributed by the functional paratope; the computational methods are first validated with known experimental data and then applied to 111 representative antibody-protein complexes. The predicted functional paratopes are mostly aromatic residues, especially Tyr and the short chain hydrophilic residues occupy the remaining minor portion. These aromatic side chains are found mostly interacting with main chain atoms and side chain carbons on the epitope sites. Furthermore, the functional paratopes are found surrounding by polar groups. About 80% of these polar groups forming favorable polar contacts with epitopes and 40% of these contacts are capable for forming direct hydrogen bonds. These results suggest that the aromatic side chains interact to main chain atoms and side chain carbons is the universal rule of natural antibody repertoire response to protein antigens by their common physicochemical properties across protein surface.
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