Promising tool to design protein

Protein Design

To discovery drugs
  • The residue communities, as important evolutionary signatures, would pave a way to engineer protiens for drug development.

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Single mutagenesis

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Complete single mutagenesis. The matrix that is computed by the SAEC method shows \(\Delta E\) — the energy difference of each mutant sequence with each mutation \(\tau\) at the ith site and wild-type (WT) sequence, negative values representing favourable while positive representing unfavourable mutations.

Sequence design

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Starting from a given WT sequence, we launch the dead-end elimination (DEE) algorithm1 to optimize the mutant sequence base on the energy-like potentials (sequence potentials) inferred from the MSA. According to the Metropolis criterion, the design protocol will accept or reject a new mutant that may occur in the WT sequence, and the change is accepted with probability as follows,

\(P=\min\{1, e^{-\Delta E/kT}\}\)

where \(\Delta E=E_{new}-E_{old}\) is the energy difference between the new and old mutant sequences, \(k\) is the Boltzmann constant, and \(T\) is the temperature.

Coupled mutations

Based on the best-so-far sequence (designed), one can conduct a signle or multiple (coupled) mutants on the WT sequence, and the energy of the mutant sequence is computed for evaluating the conbination of mutants.

References
  • [1] J. Desmet, M. D. Maeyer, I Lasters, Nature, 356(6369):539, (1992)

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