A Hierarchical Approach to Protein Molecular Evolution

Leonard D. Bogarad; Michael W. Deem

doi:10.1073/pnas.96.6.2591

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arXiv · cond-mat/9903310

A Hierarchical Approach to Protein Molecular Evolution

Leonard D. Bogarad·Michael W. Deem

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Abstract

Biological diversity has evolved despite the essentially infinite complexity of protein sequence space. We present a hierarchical approach to the efficient searching of this space and quantify the evolutionary potential of our approach with Monte Carlo simulations. These simulations demonstrate that non-homologous juxtaposition of encoded structure is the rate-limiting step in the production of new tertiary protein folds. Non-homologous ``swapping'' of low energy secondary structures increased the binding constant of a simulated protein by $\approx10^7$ relative to base substitution alone. Applications of our approach include the generation of new protein folds and modeling the molecular evolution of disease.

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Leonard D. Bogarad, Michael W. Deem. 1999-03-21. A Hierarchical Approach to Protein Molecular Evolution. https://doi.org/10.1073/pnas.96.6.2591

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