Coarse-grained lattice model simulations of sequence-structure fitness of a ribosome-inactivating protein

Biopolymers. 2008 Feb;89(2):153-9. doi: 10.1002/bip.20880.


Many realistic protein-engineering design problems extend beyond the computational limits of what is considered practical when applying all-atom molecular-dynamics simulation methods. Lattice models provide computationally robust alternatives, yet most are regarded as too simplistic to accurately capture the details of complex designs. We revisit a coarse-grained lattice simulation model and demonstrate that a multiresolution modeling approach of reconstructing all-atom structures from lattice chains is of sufficient accuracy to resolve the comparability of sequence-structure modifications of the ricin A-chain (RTA) protein fold. For a modeled structure, the unfolding-folding transition temperature was calculated from the heat capacity using either the potential energy from the lattice model or the all-atom CHARMM19 force-field plus a generalized Born solvent approximation. We found, that despite the low-resolution modeling of conformational states, the potential energy functions were capable of detecting the relative change in the thermodynamic transition temperature that distinguishes between a protein design and the native RTA fold in excellent accord with reported experimental studies of thermal denaturation. A discussion is provided of different sequences fitted to the RTA fold and a possible unfolding model.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Calorimetry / methods
  • Computational Biology / methods*
  • Computer Simulation
  • Hot Temperature
  • Models, Statistical
  • Monte Carlo Method
  • Protein Engineering / instrumentation
  • Protein Engineering / methods*
  • Protein Folding
  • Protein Structure, Secondary
  • Proteins / chemistry*
  • Ribosomes / chemistry*
  • Ricin / chemistry*
  • Solvents
  • Temperature
  • Thermodynamics


  • Proteins
  • Solvents
  • Ricin